Azarenka, who beat Serena Williams in the Flushing Meadows semi-finals, won 7-6 (9-7) 6-2 against the American's older sister to earn an enticing meeting with Australian Open champion Kenin in the last 32.
In a battle lasting just over two hours, Azarenka had to save a set point before claiming what proved to be a pivotal tie-break, the win avenging a defeat to Venus Williams in the first round of the Top Seed Open last month.
"[A] different surface was definitely challenging, but I feel like I adapted very well," Azarenka said after winning the last of the first-round matches in Rome.
"I knew it wasn't going to be easy, I knew I wasn't going to play a perfect game, but it was all about trying to find the right intention of what to do. I think it worked out.
"I felt that this was a great match for me to figure it out, the first match on clay. Venus played a really good match, it was good to see her also adapting to clay, changing and trying different shots.
"It is going to be an interesting match [against Kenin] because Sonya's been my doubles partner for the last two tournaments and we know each other quite well.
"She's a great player, she's obviously been playing exceptional this year. I feel like I'm playing all these players I've lost to before, so I'm kind of given an opportunity to redeem myself!"
Number one seed Simona Halep won 6-3 6-4 against Jasmine Paolini and will next face Dayana Yastremska, who emerged triumphant from a three-set battle against Amanda Anisimova.
Second seed and defending champion Karolina Pliskova beat fellow Czech Barbora Strycova 6-3 6-3, with Elina Svitolina and Elise Mertens also among those moving into the last 16.
There was no joy for sixth seed Belinda Bencic, though, as she was emphatically knocked out by qualifier Danka Kovinic, who earned a 6-3 6-1 win.
Azarenka, beaten in the US Open final less than a week ago, has transitioned to the clay courts in impressive fashion after beating Venus Williams and now, more impressively, Kenin.
The Australian Open champion had no answer to Azarenka's ruthlessness and near-perfection out on court in Rome, with the Belarusian claiming victory in just an hour and one minute.
Azarenka faced no break points in the entire match and made only one unforced error as she emphatically took the first set against a player who was her US Open doubles partner.
Kenin improved in the second set, forcing some long games – particularly the second, which was at deuce on five different occasions.
But Azarenka – who faces Russian Daria Kasatkina in the last 16 – simply had too much for the American and cruised to a sensational victory over the third seed,
"I think my consistency was the key to the scoreline," Azarenka told reporters. "I feel like I played really smart tennis today: I was able to use a lot of court; I was able to use a lot of different pace.
"So, I'm very happy with that. But the key was definitely being able to maintain the level that I started with."
She added, according to the WTA Tour website: "I was really more focused on what I can do today on the court, than on what she does well. So, I think that was the difference, I was able to insist on my level and insist on my pace."
Earlier, Garbine Muguruza managed to outlast American sensation Coco Gauff 7-6 (7-3) 3-6 6-3 in an absorbing contest.
Gauff, 16, appeared to be in control of the decider after an early break of serve.
But three double faults in the following game gifted Spaniard Muguruza an instant break in return, giving her the initiative to go on and seal victory.
Johanna Konta saw off Irina-Camelia Begu in fine fashion, the seventh-seeded Briton emerging 6-0 6-4, but Kiki Bertens and Petra Martic were not so impressive.
Bertens, seeded fifth, fell 6-4 6-4 to Polona Hercog, while eighth seed Martic succumbed to Yulia Putintseva in a gruelling three-hour contest, the latter eventually winning 6-3 6-7 (2-7) 6-4.
Marketa Vondrousova and Svetlana Kuznetsova were among the other victors on the day.
The world number one was leading 6-4 2-1 in Rome when, with her left thigh also heavily strapped, she pulled out of the match following talks with a trainer.
Barty's decision was precautionary as she will begin her French Open campaign in a little over two weeks' time, bidding to regain the title she won two years ago.
The scare came just hours after world number three Simona Halep announced she tore a calf muscle this week, putting the Romanian's Roland Garros prospects in some doubt.
Providing an update after the match with Gauff, which was interrupted by a rain delay, Australian Barty said: "The pain was becoming too severe so it was important to listen to my body and do the right thing knowing we have a slam."
Gauff, who had hit 12 winners to 15 unforced errors prior to her opponent's withdrawal, will now compete in her first career WTA 1000 semi-final.
Karolina Pliskova remained on course for a second Rome triumph in three years, after saving three match points to edge out Jelena Ostapenko.
The 2019 champion, who also finished runner-up last year, was 5-4 down in the final set when digging deep to hold off her 49th-ranked opponent.
The thrilling match went to a tie-break and Pliskova reeled off seven straight points after losing the opener to advance 4-6 7-5 7-6 (7-1).
"I'm just proud of how I fought," Pliskova said at her post-match news conference. "I'm happy that I stayed in there and fought until the end.
"We played last month, so I knew what was going to be happening. You can never get ready for some of the balls which she's playing."
Petra Martic stands between Pliskova and a place in the final for the third year running after the Croatian defeated Jessica Pegula 7-5 6-4.
Pegula eliminated Naomi Osaka earlier in the week but was second best against Martic, who progressed in one hour and 40 minutes.
Martic trailed 2-0 in the opening set before twice breaking Pegula to move 3-2 in front, but her opponent hit back to make it 5-5 in a tight contest.
However, Martic managed to break in the 11th game and served out the set, before showing her steeliness in the second to remain on course for a maiden WTA 1000 crown.
The world number one claimed her 27th Tour-level win of this year, seeing off Kudermetova 6-3 6-3 in 81 minutes to reach the last eight in Rome for the first time.
Barty admitted it took some time to get used to the "wow factor" of centre court in the Italian capital, but she rarely looked under threat as she moved to 13-2 on clay in 2021.
The Australian would have faced Aryna Sabalenka for the third tournament in a row had it not been for a sterling performance from Gauff, who won 7-5 6-3 to secure a fourth quarter-final this year.
"Coco has shown that she loves to bring her best tennis against the players that challenge her the most," said Barty, who has never played against the American teenager. "She's played an exceptional tournament thus far. She's got the ability to take the game on. She's aggressive, she can run, she can trust her legs.
"I think it's going to be important for me to try to get the match back on my terms as often as possible. I know when they're in her patterns, the way she likes to play, she's extremely dangerous and very good at what she does. I think it's going to be a new challenge, a clean slate for both of us."
Matters were more difficult for reigning French Open champion Iga Swiatek, who saved two match points before beating Barbora Krejcikova 3-6 7-6 (7-5) 7-5 in a contest lasting nearly three hours.
Powerful serving from Krejcikova and some errant shots from Swiatek gifted the Czech the chance to serve out a straight-sets win, but Swiatek held firm before taking the tie-break.
Swiatek persisted with a drop shot that seemed to cause difficulties for her and her opponent before Krejcikova's aim went awry at the end of the decider.
"I had fun when I played drop shots because today I felt them really good," said Swiatek, who will now face fifth seed Elina Svitolina after her 6-4 6-2 beating of Garbine Muguruza.
"I asked myself a question, what would annoy me in that situation? So, I tried to do that. So, yeah, sometimes it didn't look pretty, but I'm happy that I could do that. One year ago I wouldn't even come up with a solution like that. That's a progress."
Jessica Pegula followed up her shock win over Naomi Osaka by defeating Ekaterina Alexandrova in straight sets. She will now face Petra Martic, who came from a set down to defeat world number 44 Nadia Podoroska – conqueror of Serena Williams on Wednesday.
Ninth seed Karolina Pliskova, who beat Vera Zvonareva 7-5 6-3, will face Jelena Ostapenko following her three-set defeat of Angelique Kerber.
The world number one advanced to the last eight for a 14th straight year at the tournament with a 7-6 (9-7) 6-3 victory over Krajinovic.
Djokovic had not faced Krajinovic in more than a decade and said it was difficult facing off against one of his closest friends.
"It was one of the longest sets of my career," he said of the first set which lasted an hour and 27 minutes. "It is never easy to play against one of your best friends of so many years.
"We have only played 10 years ago in Serbia and he has changed as a person and as a player. It is rare that we have not played against each other in this decade. We trained several times together and we have played the Davis Cup together; it was good to play against him.
"Janko Tipsarevic [Krajinovic's coach], a Serbian tennis legend, is doing a great job with him. He's in the top 30; I know he's in shape.
"I did not start the game as I wanted. I made many unforced errors, but we must congratulate him for pushing me to the limit."
Djokovic saved five of six break points to seal the win after two hours and seven minutes, setting up a quarter-final clash with Dominik Koepfer.
He attacked Krajinovic's forehand with gusto and delivered a string of drop shots throughout the first set, but that game plan did not come off when holding two set points at 5-4 on his opponent's serve.
Krajinovic then started the tie-break strongly, storming into a 4-1 lead, before Djokovic powered back and took advantage of an error from his opponent to seal the set at the fifth time of asking.
Djokovic wasted little time moving through the gears at the start of the second set, driving forehands down the line to break serve at 1-1. He maintained his advantage to reach 5-3 before breaking serve again to seal the win.
Djokovic needs to reach the semi-finals in Rome to ensure Daniil Medvedev cannot usurp him atop the ATP rankings next week, and he made a solid start with a 6-3 6-2 victory over another Russian in the second round.
Karatsev did initially pose a threat, with both players breaking at the first opportunity, but Djokovic's superiority gave him the edge in the first set and then saw him cruise in the second.
Djokovic – who will face either Stan Wawrinka or Laslo Djere next – acknowledged he undoubtedly benefited from Karatsev's wastefulness, however.
"You never know with him," Djokovic said. "If he's feeling the ball, he can be very dangerous because he stays so close to the line, puts pressure on his opponents.
"He was missing a lot of balls today, though. He gave me a couple of breaks there in the first and second sets, but I'll take this win for sure.
"It's a straight-sets win against a quality opponent, and I'm looking forward to the next challenge."
Fifth seed Casper Ruud also progressed to the last 16 but was tested by Botic van de Zandschulp, with the Norwegian eventually coming through 6-7 (4-7) 6-2 6-4.
But Andrey Rublev, who had won six of his previous seven matches, was a surprise second-round casualty as he fell to Filip Krajinovic in straight sets, with the Serbian claiming a 6-2 6-4 win.
Canadians Felix Auger-Aliassime and Denis Shapovalov were the other seeds to reach the last 16 on Tuesday. The former was pushed hard by Alejandro Davidovich Fokina in his 4-6 7-6 (7-2) 6-2 success, while the latter could face Rafael Nadal next up.
Meanwhile, across seven first-round matches, Cameron Norrie, Jannik Sinner and Diego Schwartzman were the biggest names to advance, though 11th seed Hubert Hurkacz was dumped out by the unseeded David Goffin.
Djokovic, playing his first match since a shock loss to Aslan Karatsev in the semi-finals of the Serbia Open on home soil, dispatched American Fritz 6-3 7-6 (7-5) on Tuesday.
The world number one, who missed the Madrid Open, won the first three games of the match and saved both break points he faced in the opening set.
Fritz had broken for a second time in the second set to level at 5-5 when the rain came at the Foro Italico, but the top seed was able to come back out on court to finish off the job and will face Cameron Norrie or Alejandro Davidovich Fokina in the third round.
Auger-Aliassime secured the third victory over a top-10 opponent in his fledgling career, beating eighth seed Schwartzman 6-1 6-3 to move into round three.
The 20-year-old Canadian only needed 64 minutes to send the Argentine packing, converting five of the six break-point opportunities he earned.
Matteo Berrettini saw off Nikoloz Basilashvili 4-6 6-2 6-4 in the first round less than 48 hours after the Italian was beaten by Alexander Zverev in the Madrid Open final.
Gael Monfils was unable to win his first match since the Australian Open, as Lorenzo Sonego got the better of the fit-again Frenchman, who had been sidelined with a calf injury, 6-4 5-7 6-4.
Reilly Opelka moved into the last 16 with a 6-4 6-4 defeat of Lorenzo Musetti, while Pablo Carreno Busta's withdrawal due to lower back pain handed Kei Nishikori a walkover.
Daniil Medvedev and David Goffin were unable to start their second-round matches due to the weather in Rome.
Tabilo stunned Djokovic with a straight-sets victory in the third round on Sunday, winning 6-2, 6-3 in his maiden ATP Tour clash with the Serbian.
The Chilean advances to the fourth round at a Masters 1000 event for just the second time after Indian Wells in 2023, with Djokovic unable to explain his struggles in Rome.
"I just wasn't able to find any kind of good feelings on the court, to be honest, striking the ball. I was completely off," he said.
A six-time champion in Rome, the 36-year-old won his opening-round match at the ATP Masters 1000 event against Corentin Moutet.
However, Djokovic was inadvertently hit on the head by a falling water bottle when leaving the court after that victory.
Whether that incident impacted his performance against Tabilo remains to be seen.
"I don't know, to be honest. I have to check that," he said. "Training was different. I was going for [a] kind of easy training yesterday.
"I didn't feel anything, but I also didn't feel the same. Today under high stress, it was quite bad – not in terms of pain, but in terms of this balance.
"Just no coordination. Completely different player from what it was two nights ago. Could be. I don't know. I have to do medical checkups and see what's going on."
Tabilo's next opponent will be Karen Khachanov, who saw off Francisco Cerundolo 6-2, 6-4, while Djokovic is made to wait for his 1100th match win.
The world number one remains on course for a record-breaking 36th ATP Masters 1000 title but was forced to save two set points in the opener against Norway's Ruud.
Djokovic will contest Monday's final against Denis Shapovalov or Diego Schwartzman, who stunned Rafael Nadal in the quarter-finals to end the clay court maestro's similar designs on title 36 in the highest tier of ATP Tour events.
Ruud has impressed on clay this season, boasting a tour-leading 12 wins on the red stuff.
The 21-year-old was targeting a third final in four events on the surface and pocketed an early break before staying cool under pressure on the forehand side to repel two break-back points at 3-2.
It meant Ruud served for the set at 5-4 but he was unable to convert as Djokovic got back on terms with a fabulous drop shot winner.
The 17-time grand slam champion shut the door on Ruud three times during a 12-minute 11th game and the pressure told on his opponent, with a misfired forehand conceding the set.
Djokovic then put his foot down with some authoritative ground strokes to break for 4-2 in the second.
He continued to batter Ruud to the forehand corner and completed the victory in two hours and 11 minutes.
An imperious 30-1 record in 2020 must now be set alongside Djokovic's less-than-impressive recent efforts in the Rome showpiece.
Despite being a four-time winner in the Italian capital, defeats to Andy Murray, Alexander Zverev and Nadal mean he has finished as runner-up in three of the past four years.
World number one Djokovic came from a set down overnight to beat Stefanos Tsitsipas 4-6 7-5 7-5 early on Saturday, before returning to the court to face Italian Lorenzo Sonego in the evening.
The Rome crowd raucously rallied behind Sonego, who beat Andrey Rublev earlier in the day, and the 26-year-old rose to the challenge but eventually fell to a 6-3 6-7 (5-7) 6-2 defeat.
Djokovic had match points before serving for it at 6-5 in the second set, yet it was to prove a stirring game as the noisy home crowd encouraged Sonego, who snatched a gutsy break. The tie-break looked set to be wholly one-sided when Djokovic raced 3-0 ahead, but it was soon back on serve, partisan spectators at the Foro Italico roaring in delight at a double fault from the Serbian.
From 4-2 behind, Sonego surged to 6-4 ahead in the tie-break. He failed to convert a first set point when ripping a forehand into the net, but the set was his when Djokovic sent a backhand service return long.
Sonego then had 0-40 against the Djokovic serve at the start of the decider, but he could not force the break, and the top seed gained strength from that escape, eventually cruising to victory.
Five-time Rome champion Djokovic said on Amazon Prime: "I bounced back very well after the second set. Maybe if he started with a break up in the third, things would look differently. I also had my chances and I only had myself to blame for not closing the match in straight sets.
"But he's a quality player, very dynamic, it's not easy to play against him and obviously he had the crowd behind him. It was an electric atmosphere. In the end I managed to close out the match really well."
Looking ahead to tackling Nadal, Djokovic said: "I need to recover. Hopefully I'll have fresh legs because that's what I definitely will need and it's necessary to have a chance against Rafa. He also had some tough matches [this week] and hopefully I'll be fresh and I'll give it all."
While Djokovic and Sonego thrashed away into the night, nine-time champion Nadal had no such workload issues on Saturday.
Nadal beat Alexander Zverev on Friday to set up a semi-final against American Reilly Opelka, and the Spaniard snatched a 6-4 6-4 win from that contest to reach the title match.
It has been a frustrating season to date for the Serbian, who reached a final in Belgrade last month before being beaten by rising star Carlos Alcaraz in Madrid earlier in May.
Yet with Rafael Nadal out of the picture, Djokovic is the clear favourite heading into the Internazionali d'Italia semi-finals, after he beat Auger-Aliassime 7-5 7-6 (7-1) on Friday.
The win not only tees up a semi-final against Casper Ruud, who saw off Nadal's conqueror Denis Shapovalov 7-6 (9-7) 7-5, but also ensures Djokovic will spend a 370th week at the top of the ATP rankings, after he slipped below Daniil Medvedev in the live standings.
Djokovic will add 360 points to his total for reaching the last four, and he now has a milestone 1,000th Tour-level win in his sights when he takes on Ruud for a place in the final. The 34-year-old has won a record 37 Masters 1000 titles so far in his career, including five in Rome.
"I thought it was high-level tennis," Djokovic said. "[Auger-Aliassime] did ask me to raise the level and I had to play consistently well.
"I thought I could have finished the job earlier, but credit to him for fighting back.
"I know Felix well. He's been around the top of the men's game for quite a few years. He's got a lethal serve, honestly. He's hitting his spots in the box incredibly well with the serve, and it was not easy for me at all to return.
"He's also returning well, he's moving well. He's a very complete player."
The other semi-final will see second seed Alexander Zverev, who beat Cristian Garin 7-5 6-2, take on Stefanos Tsitsipas.
Greek Tsitsipas overcame Jannik Sinner 7-6 (7-5) 6-2, becoming the first player to reach 30 wins on the ATP Tour in 2022.
"We have similar game styles but he is one of the most difficult players to play against on the Tour," Tsitsipas said, previewing his clash with Zverev.
"I have a lot of respect for him. He has achieved a lot so far and I try and look up to him with the things he has achieved."
The Serbian, who has not played since the semi-finals in Monte-Carlo, made a slow start, falling 1-3 behind in the first set, but recovered to take the first match.
Moutet could not regain his level, and Djokovic dropped only one set as he cruised through the second match to advance after one hour and 26 minutes.
Djokovic, a six-time champion in Rome, will take on Alejandro Tabilo in the third round after the Chilean beat Yannick Hanfmann 6-3, 7-6 (7-4).
Data Debrief: Still on top
Djokovic now has 23 wins in ATP-1000 events since turning 35. He eclipses John Isner (22) for the outright second most wins in such tournaments since the introduction of the format in 1990; only Federer, with 51, has more.
The Serbian will have the opportunity to clinch his 1100th match win in the third round as he chases his first trophy of the season.
The reigning champion was in trouble when play was halted in the quarter-final clash on Friday, trailing by a set and a break before persistent rain forced an early end to proceedings.
However, Djokovic was able to get back on level terms before the duo played out a see-saw deciding set that twice saw Tsitsipas hold control.
The sixth seed – seeking a first win over the world number one on clay at the third attempt – even had the chance to serve out for the match when 5-4 ahead, only to falter with the finishing line in sight.
Djokovic instead claimed three games in a row to finally prevail after three hours and 16 minutes on court. He has little time to recover, though, as his semi-final match is scheduled for later on Saturday.
Next up will be Italian Lorenzo Sonego, the home favourite having produced a comeback of his own to see off Andrey Rublev 3-6 6-4 6-3 in another contest held over from Friday.
Djokovic will hope for a more straightforward encounter after being pushed all the way by Tsitsipas, who will rue his missed chances.
The Greek led 2-1 in the final set after clinching a break that led to his opponent throwing his racket in frustration, earning him a code violation.
He had openings to extend that advantage in the fifth game before losing his serve in the eighth, only to quickly forge his way back in front to move to the brink.
Yet a gripping set of tennis that saw a combined total of 16 break-point opportunities somehow went Djokovic's way, a memorable victory wrapped up when Tsitsipas slashed a tired-looking backhand wide.
Top seed Djokovic had not played since he was disqualified at Flushing Meadows earlier this month after hitting a line judge with the ball in the fourth round against Pablo Carreno Busta, his first defeat of the season.
But he returned to action in typically composed fashion in Italy, dispatching world number 87 Caruso 6-3 6-2.
Djokovic, who received a bye for round one, took just 84 minutes to claim the victory and will face Mario Cecchinato or Filip Krajinovic in the last 16.
The four-time Rome champion did not face a single break point throughout Wednesday's encounter, converting three of the eight Caruso offered up.
Having clinched the opening set at the second time of asking, Djokovic crucially nosed himself ahead in the second when he broke Caruso in the third game.
At one point during the 11-minute game, Djokovic complained about noise from the mainly empty stands. While fans are not allowed, coaches and tournament officials were in attendance.
"Which one?" the umpire replied, to which a frustrated Djokovic responded: "Which one? There's 10 people in the stands."
However, unlike in New York, Djokovic this time kept a lid on his temper and had the match all but won when he broke the Italian again to make it 5-2, the world number one then duly wrapping up victory with his first match point.
Reigning champion Djokovic, who is seeking a sixth triumph in Rome, struggled to get going against Tsitsipas and trails 6-4 2-1 ahead of the scheduled resumption of play on Saturday.
The top seed lost serve in the first game and continued to make some uncharacteristic errors that saw him trail 4-1 at one point.
While Djokovic did earn a first break in the sixth game, Tsitsipas stood firm to take the opening set and was in total control when again breaking his opponent early in the next set.
However, soon after the Greek had opened up a 2-1 advantage, the worsening conditions led to a pause in proceedings and organisers were eventually forced to bring the day's play to an end.
Djokovic, who converted just one of his six break point opportunities, will return to the court on Saturday and will need to improve if he is to join Rafael Nadal in the final four.
Nadal exacted some revenge on Alexander Zverev earlier on Friday to reach the semi-finals for a 12th time.
The Spaniard lost to Zverev at the same stage of the Madrid Open seven days ago but responded to questions over his form by easing through this latest encounter.
Nadal, who saved two match points before beating Denis Shapovalov on Thursday, raced 4-0 ahead in the first set against Zverev and had little trouble seeing the job through.
Aiming for a record-extending 10th title in the Italian capital, Nadal saved all eight break points he faced in the second set to advance 6-3 6-4 in two hours.
"I played more solid than Madrid. Conditions are different," he said in his post-match interview. "Here the conditions are a little more normal. I was able to control a little bit more."
"I'm happy. I played a very solid match with not many mistakes, playing the way that I have to. It's an important victory for me against a great player."
Nadal will face Reilly Opelka for a place in the final, the American beating qualifier Federico Delbonis 7-5 7-6 (7-2) to reach his first ATP Masters 1000 semi-final.
Opelka entered the tournament on a six-game losing streak, but he kept his good run going in Rome by earning the only break of the opening set in the 12th game.
Both players held throughout the second set and it was big-serving Opelka who prevailed 7-2 in the tie-break.
The day's other quarter-final between Lorenzo Sonego and Andrey Rublev also fell victim to the bad weather and will get under way on Saturday.
The world number one said he played a "perfect set" to race through the opener, before coming from a break down in the second to earn a 6-0 7-6 (7-5) victory in Sunday's final.
Djokovic made it a record-extending 38th Masters 1000 title in what was his 55th final at this level, and it was his sixth triumph at this event in the Italian capital.
At 34 years, 11 months and 23 days old, Djokovic is 10 days older than the previous oldest Rome champion, Rafael Nadal, who took the title last year.
He boosted his head-to-head record to 7-2 against Greek star Tsitsipas, winning their last six matches and all five they have contested on clay, including last year's French Open final where Djokovic came from two sets behind to scoop the grand slam. This victory clearly augurs well for Djokovic's upcoming title defence in Paris.
Djokovic broke serve to love in the opening game, Tsitsipas swatting a volley into the net to hand over the early advantage and set the tone for a wildly one-sided set.
Tsitsipas broke to lead 3-1 in the second set and he served for it at 5-3 but was broken to 15, sending a forehand wide on game point. The tie-break that soon followed was hard fought, with Tsitsipas looping a backhand long on match point as Serbian Djokovic earned the trophy once again.
Reflecting on his fast start, and his first title of 2022, Djokovic said on Amazon Prime: "I pleasantly surprised myself, I can say, even though I had a clear game plan and strategy coming into the match. I knew what to expect from the other side so I knew what I had to do, but I did play a perfect set, no doubt about it.
"After that it was a little bit tight, the beginning of the second for me. He used it, and at this level one or two points can turn a match around and he was back in the game. At 4-1 up for him and 30-40, the match could have easily gone into a third set, but I somehow managed to find the right shots at the right time to come back in the game, and the tie-breaker, I guess I was just an inch better, maybe calmer, and it was a tight tie-break for both of us."
Ahead of the French Open, which gets under way next Sunday, Djokovic is feeling in great shape for his title defence. Having missed the Australian Open in January in a deportation drama, Djokovic will head to Paris as a major rival to teenage sensation Carlos Alcaraz.
Should Djokovic triumph at Roland Garros, he would match Nadal's men's record of 21 grand slams.
"I've been building my form in the last couple of weeks and like the previous years I knew that my best shape on clay was usually coming around Rome time," Djokovic said.
"So it couldn't be a better time, coming into Roland Garros with a title at this wonderful tournament. I'm going to Paris with a lot of confidence."
Tabilo recorded the biggest win of his career with a dominant performance, winning 6-2, 6-3 in his maiden ATP Tour clash with the Serbian.
Djokovic, who was hit on the head by a water bottle following his second-round win over Corentin Moutet, struggled to get going as he saw his serve broken four times.
Tabilo clinched the opening set in style, making few errors, and Djokovic failed to mount a comeback in the second, with double faults costing him at key moments, including one on the final break serve.
The Chilean advances to the fourth round at a Masters 1000 event for just the second time after Indian Wells in 2023. His next opponent will be Karen Khachanov, who saw off Francisco Cerundolo 6-2, 6-4.
Data Debrief: Big winner
Tabilo is the second player from Chile to defeat the World No.1 in ATP-1000 events after Fernando Gonzalez, who defeated Lleyton Hewitt at the Hamburg Masters in 2003, since the introduction of the format in 1990.
He is also the first Chilean to defeat a World No. 1 since Fernando Gonzalez beat Roger Federer at the 2007 Nitto ATP Finals Round Robin.
Djokovic, meanwhile, is made to wait for his 1100th match win.
The world number one was disqualified from his last-16 match against Pablo Carreno Busta after striking a linesperson with the ball.
The Serbian, who said he was "extremely sorry" for his actions, was left feeling "sad and empty" over the incident, which saw him take a ball from his pocket and hit it behind him after dropping serve.
The 33-year-old is back in action this week at the Internazionali d'Italia in Rome, where he will start against either Tennys Sandgren or Salvatore Caruso after being given a bye in the first round.
Speaking to reporters on Monday, Djokovic said: "Of course, it was a shock to finish the US Open the way it was finished. It was the first time in my career that something like this happens.
"Of course, it could have happened earlier in my career, you know, could have happened to many players.
"The ball hits a line judge, it was just unfortunate that I hit the line umpire in a very awkward place. There was a lot of speculation and discussions whether it was deserved or not, I accepted it and I moved on.
"I cannot promise or cannot guarantee that I will never ever do anything similar to that in my life. I'm going to try my best, obviously, but anything is possible in life.
"I accepted it, I had to move on and that's what I did. Of course, I did not forget about it, I don't think I will ever forget about it, these things stay in your memory for the rest of your life, but I don't think I will have any major issues coming back to the tour and being able to perform well and hit the tennis ball during the point.
"I checked on [the line judge] after the match, she said that she was fine, that there were no injuries. I felt really sorry to cause the shock and drama to her, she didn't deserve that in any way, she's obviously volunteering as well, she loves tennis and has been there for quite a few years.
"It's unfortunate for both of us to experience that. It was very awkward and disappointing for me to finish off the US Open that way because I felt very good about myself, my game, I had won the Western and Southern Open.
"I came into the fourth round feeling really good and hitting the ball really nicely, and ready in every aspect. It was very unexpected and very unintended as well, to hit her.
"But when you hit the ball like that as I hit it to have a chance to hit someone who is on the court and the rules are clear when it comes to that."
Djokovic, who was unbeaten in 2020 prior to the US Open, has won the Internazionali d'Italia on four occasions, the last of which came in 2015.
The world number one defeated Diego Schwartzman 7-5 6-3 in Monday's final, the same scoreline he had recorded to defeat Casper Ruud in the last four to reach a 10th final at the tournament.
Djokovic's 36th ATP Masters 1000 title – which moved him ahead of Rafael Nadal into the outright lead - and 81st overall on the ATP Tour was an ideal response after he was disqualified from the US Open.
That infamous default came after he struck the ball at a line judge during his fourth-round match against Pablo Carreno Busta in New York this month.
After overcoming a nervous start against Schwartzman, victory gave Djokovic a fifth title in Rome, though it was his first since 2015 – having lost three finals and suffered a semi-final exit in the previous four years.
He will now bid to end the French Open dominance of Nadal, who stunningly went out to Schwartzman in the quarter-finals in Italy, when the upcoming last grand slam of the year begins in Paris.
Djokovic won the first set despite losing the first three games, recording 18 unforced errors and seeing a set point go begging at 5-4 when his Argentine opponent unleashed a superb cross-court forehand.
He had three more opportunities in Schwartzman's next service game, though, taking the last of those to move ahead.
A comeback looked to be on the cards when Djokovic sent a forehand wide to give Schwartzman a break in the first game of the second set.
But the Serbian, who converted five of his nine break points on the day, struck straight back and decisively moved 5-3 ahead later in the set with a fine backhand down the line.
After saving two match points, Schwartzman sent a shot wide on the next as Djokovic – who may have expected a different outcome when he fell a double break down to start the match – looked relieved as he raised his arms and congratulated his opponent on a superb tournament.
Spanish 19-year-old Alcaraz claimed his fourth title of the season at the Madrid Open on Sunday, defeating world number three Alexander Zverev in the final after overcoming Djokovic and Rafael Nadal in his two previous matches.
The teenager has surged up to a career-high sixth in the world rankings as a result, though he opted against competing at this week's Internazionali d'Italia with the French Open rapidly approaching.
"He definitely is special," said Djokovic, who will begin his campaign in Rome against Aslan Karatsev on Tuesday.
"Already he's breaking a lot of records as a teenager, winning two Masters events this year, a couple of 500s. So far, he's the best player in the world, no question, this year with the results that he's been doing.
"The way he was dealing with the pressure... In our match few days ago, how calm he was all the way until the [end] was impressive.
"He deserved to win the trophy. Everything about his game is really impressive. He's a really complete player, can play equally well offensively and defensively. He's the talk of the sport."
Djokovic is yet to win any silverware this season and possesses a 7-4 record, but feels as though he has turned a corner ahead of Roland Garros, where he beat Stefanos Tsitsipas to win his second French Open title last year.
"I think it's closer to [my] desired level every week," he explained. "Madrid, even though I lost in the semi-finals, I still think I played really good tennis, felt physically 100 per cent, even after an almost three-and-a-half-hour battle against Alcaraz.
"I recovered well the next day, was ready to go. That's a positive and encouraging factor prior to Rome and also, of course, the big goal, which is Paris.
"I think I'm [going] in the right direction. I know I can always play better, and I know that I'm very self-critical on the court. At the same time, realistically looking, I think the tennis, quality of tennis, level of tennis, is really high now.
"Hopefully I can maintain that level throughout this week and build, go deep in this tournament hopefully — that's the goal — and come to Paris well-prepared."
