Djokovic slumped out in the second round on Tuesday when he lost 6-3 6-7 (5-7) 6-1 to world number 46 Alejandro Davidovich Fokina.
The Serbian's status as an unvaccinated player has limited his ability to compete on the ATP Tour this year and he has played in just one tournament so far, getting to the quarter-finals in Dubai.
Yet his preparations for the French Open, which starts at the end of next month, hardly got off to a good start as he made 51 unforced errors in what was still, despite his rustiness, a surprise defeat.
"I didn't like the way I felt physically in the third. I just ran out of the gas completely," Djokovic told the media.
"Just couldn't really stay in the rally with him. I mean, if you can't stay in the rally, not feeling your legs on the clay, it's mission impossible.
"I'm going to look with my team into reasons why that was the case and go back to the drawing board. Hopefully next week will be better in Belgrade."
Though Djokovic has won twice in Monte Carlo, it has not been a happy hunting ground for him in recent years. He has not advanced past the quarter-final stage since 2015.
He added: "It's going to take some time for me to really feel my best on the clay.
"That's historically always been the case. [I have] never played very well in the opening tournaments of the clay season.
"But it's okay. Obviously it is what it is. I have to accept the defeat and keep working."
While unhappy with his own performance, Djokovic had nothing but praise for his opponent.
"I would like to congratulate Alejandro. He was the better player," Djokovic said. "He managed to find a better rhythm I think in the first two sets. I was hanging on the ropes the entire match. I was really chasing the result constantly.
"I always believed that I could come back and win the match, and I stayed there even though a lot of things were against me in terms of how I felt on the court. Game-wise, physically I was just far from my best.
"I expected this match to be [a] really tough match, [a] physical battle, and that's what it was. Unfortunately I'm on the shorter end of the stick, and my week ends here."
Djokovic's defeat also means a mouthwatering contest with teenager sensation Carlos Alcaraz, who he might have met in the quarter-finals, will not be taking place.
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.
The draw for the tournament that begins on Sunday served up the appetising prospect of a tussle between the reigning French Open champion and a player many expect to enjoy huge Roland Garros success.
Alcaraz, 18, last week became the youngest men's champion at the Miami Open, and he has soared to number 11 in the ATP rankings after sitting outside the top 100 at this time 12 months ago.
He won an ATP 250 tournament on clay last year in Umag, and an ATP 500 on the surface in Rio de Janeiro in February, but earning a Masters 1000 hard court title in Miami highlighted the scale of Alcaraz's rapid improvement.
Both he and Djokovic will receive a first-round bye in Monte Carlo, and they must then win twice to set up a meeting at the last-eight stage.
Alcaraz may have to beat the in-form Indian Wells champion Taylor Fritz in the third round, with Marin Cilic and Sebastian Korda also potential early opponents for the young Spaniard.
Djokovic will not be taking a quarter-final place for granted, either. If he navigates his opening match, the Serbian could face a dicey third-round clash with Spain's Roberto Bautista Agut or the player to whom he lost at the last-16 stage last year, Britain's Dan Evans.
Rafael Nadal is absent after suffering a stress fracture of a rib during his Indian Wells final defeat to Fritz.
Djokovic lost to Medvedev in the US Open final in September, with that defeat ending his hopes of a calendar Grand Slam.
But the Serbian, whose semi-final win over Hubert Hurkacz ensured he will be the year-end world number one for a record seventh time, got his revenge in France.
It marks a fifth title of the year and a sixth triumph at this event for Djokovic, who did not compete in the tournament last year – Medvedev winning it in his place.
The 34-year-old had it far from his own way, with Medvedev instantly going a break up, and although Djokovic hit back to draw level at 2-2, the world number two held off a second break point before nosing himself ahead at 4-3.
Yet having served out the first set at the first time of asking, the US Open champion slipped up in the fourth game of the second as Djokovic reeled off some superb returns, and he did not look back.
With the momentum and crowd on his side, Djokovic broke Medvedev twice in quick succession in the decider, and although he was denied claiming the win on his serve, it merely delayed the inevitable.
Medvedev's powerful serve was not enough, with Djokovic keeping his composure to seal a record-setting 37th Masters 1000 title with a sublime forehand into the corner of the court following a draining rally.
US senator Rick Scott claimed Djokovic has been refused permission by the US Department of Homeland Security for a vaccine waiver and urged president Joe Biden to intervene on behalf of the Serbian and "fix this NOW".
Scott was backed by fellow senator Marco Rubio, who wrote on Twitter: "@DjokerNole [Djokovic] shouldn’t be prohibited from playing in the @MiamiOpen because of unconstitutional vaccine mandates.
"@POTUS [Biden] should immediately grant Djokovic a waiver to the vaccine mandate for international travellers."
Djokovic has refused to be vaccinated against COVID-19 and that stance has cost him places in two grand slam tournaments, being deported before last year's Australian Open and then denied permission to compete at the US Open later in the season.
It has also meant he has had to miss regular tour events in the United States, which demands international travellers are fully vaccinated.
Scott and Rubio are both senators for Florida, and accordingly their focus is on the Miami Open, which runs from March 22 to April 2.
More pressingly for the 35-year-old Djokovic, the Indian Wells tournament begins in the coming week, with main draw singles matches getting under way on Wednesday.
A statement posted on the US Open Twitter page confirmed support for the 22-time grand slam winner.
It read: "Novak Djokovic is one [of] the greatest champions our sport has ever seen.
"The USTA and US Open are hopeful that Novak is successful in his petition to enter the country, and that the fans will be able to see him back in action at Indian Wells and Miami."
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.
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.
With the ATP Tour set to resume after the coronavirus-enforced break, world number one Djokovic has confirmed he will arrive in New York on Saturday.
Though Djokovic will be present at the US Open, defending champion Rafael Nadal will not play due to concerns over coronavirus, while world number four Rodger Federer is taking time out to recover from knee surgery.
The Western and Southern Open – usually held in Cincinnati – will take place at Flushing Meadows between August 22 and 28, with the US Open starting at the same venue on August 31. Both tournaments will be played behind closed doors.
Djokovic came under criticism for being the driving force behind the Adria Tour, which drew large crowds before the event was cancelled after Grigor Dimitrov tested positive for COVID-19.
Borna Coric and Djokovic subsequently returned positive tests, with the Serbian claiming he was the subject of "a witch hunt".
However, Djokovic will now return to action in August, though the 33-year-old acknowledged it was tough to make up his mind.
"I am happy to confirm that I will participate at the Western and Southern Open and US Open this year," a post on Djokovic's official website read.
"It was not an easy decision to make with all the obstacles and challenges on many sides, but the prospect of competing again makes me really excited.
"During my career, I have played some of my best matches at the USTA Billie Jean King National Tennis Center.
"I am aware that this time around it will be very different with all the protocols and safety measures that are put in place to protect players and people of New York."
Djokovic insisted he has fully recovered from coronavirus and has done all he can to ensure the safety of himself and those around him.
"I have trained hard with my team and got my body in shape so I am ready to adapt to new conditions," the post continued.
"I've done all the check-ups to make sure I am fully recovered and I am ready to get back on court fully committed to playing my best tennis.
"I respect and appreciate everyone taking time, effort, and energy to organise these two events for the tennis players to be able to go back to their working field."
Women's world number one Ash Barty has will not take part in the US Open, while top-10 players Elina Svitolina and Kiki Bertens have also withdrawn.
World number two Simona Halep is set to decide on her participation following the Prague Open, which finishes on Sunday.
The six-time champion avenged his defeat by Khachanov in the 2018 Championship match by running out a commanding 6-4 6-1 winner.
That gave Djokovic his 11th straight victory in the French capital, where he is unbeaten since that 2018 defeat, while he has also won each of his last 11 Tour-level matches.
The Serbian, who has triumphed in Tel Aviv and Astana during that streak, set up a last-eight clash with Lorenzo Musetti after the Italian came from behind to stun third seed Casper Ruud 4-6 6-4 6-4.
The Naples champion recorded his maiden top-five victory at the seventh attempt, while he hit 37 winners to advance to his first ATP Masters 1000 quarter-final.
Meanwhile, world number one Carlos Alcaraz won five out of seven break points as he breezed past Grigor Dimitrov 6-1 6-3 to reach the last eight in Paris for the first time.
There, he will play Holger Rune after the Stockholm champion defeated seventh seed Andrey Rublev in straight sets.
Fifth seed Stefanos Tsitsipas overcame Corentin Moutet 6-3 7-6 (7-3) to reach his 14th quarter-final of the season, where he will face Tommy Paul after the American denied Pablo Carreno Busta 6-4 6-4.
Felix Auger-Aliassime was a commanding 6-1 6-3 victor over Gilles Simon. The eighth seed will take on Frances Tiafoe, who defeated Alex De Minaur 6-3 7-6 (7-5).
Djokovic, the world number one, continued his impressive run in New York, where the ATP 1000 event is being held instead of Cincinnati due to the coronavirus pandemic.
The Serbian may have been expecting to have Medvedev awaiting him in the last four, but the Russian exited.
Meanwhile, Stefanos Tsitsipas is also into the semi-finals.
DJOKOVIC RACES THROUGH
Djokovic needed just 62 minutes to breeze past Jan-Lennard Struff 6-3 6-1 to reach a record-equalling eighth Western & Southern Open semi.
The 17-time grand slam champion, who is yet to drop a set at the tournament, improved to 21-0 this year.
Djokovic tied Jimmy Connors, Stefan Edberg, Roger Federer and Bill Talbert's semi-final totals at the ATP 1000 tournament.
BAUTISTA AGUT BEATS MEDVEDEV
Defending champion and last year's US Open runner-up, Medvedev departed in the quarter-finals.
Medvedev, the third seed, was beaten by eighth seed Roberto Bautista Agut 1-6 6-4 6-3.
Bautista Agut has lost eight of his 11 meetings with Djokovic, but won two of their three clashes last year.
TSITSIPAS THROUGH AS RAONIC SAVES MP
Tsitsipas was only on court for 38 minutes before Reilly Opelka retired due to a right knee injury.
Opelka led 6-5 against the fourth seed before retiring due to the injury.
Tsitsipas will face Milos Raonic, who saved a match point before overcoming Filip Krajinovic 4-6 7-6 (7-2) 7-5.
Raonic saved a match point in the 10th game of the third set, winning 11 of the final 13 points to advance.
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."
Djokovic has played only once on the ATP Tour since losing the US Open final to Daniil Medvedev on September 12.
That defeat at Flushing Meadows ended Djokovic's hopes of achieving a calendar Grand Slam, though the Serbian has returned to action for the final few weeks of the 2021 season.
With the ATP Finals coming up, Djokovic headed to Paris looking to regain the title he claimed in his last appearance in the tournament back in 2019. He needed three sets, but overcame Marton Fucsovics 6-2 4-6 6-3 in his first match.
He has won the Paris Masters on five occasions and is the top seed this time around, with defending champion Medvedev seeded second.
Monfils, seeded 15th, beat Miomir Kecmanovic and Adrian Mannarino en route to the last 16, but confirmed to the media on Thursday that he had been advised not to continue.
Djokovic will face the winner of Cameron Norrie, who recently triumphed at Indian Wells, and Taylor Fritz in the quarter-finals.
The field has already been cleared of third seed Stefanos Tsitsipas, who retired hurt when facing Alexei Popyrin on Wednesday.
Serbian Djokovic defeated Pole Hubert Hurkacz 6-3 6-4 to reach his seventh Madrid Open semi-final, where he will meet Alcaraz, who overcame Rafael Nadal 6-2 1-6 6-3 on Friday.
Victory made 19-year-old Alcaraz the first teenager to beat record 21-time grand slam winner Nadal on clay on the ATP Tour.
Alcaraz has won his last five matches against top-10 opponents and next faces world number one Djokovic for a place in the final in the Spanish capital.
Djokovic was quick to hail Alcaraz, who will play in his third ATP Masters 1000 semi-final on Saturday.
"There are many things that are special about him," Djokovic said in a news conference.
"In the last decades, we have had some incredible champions [as teenagers] like Michael Chang. But, nowadays, we're not used to seeing someone who is a teenager and already breaks into the top 10 and plays at such a high level.
"His growth, his improvement and his trajectory, especially in the last six months, have been incredible.
"He is a very nice guy off the court. I had the opportunity to train with him and spend a little time off the court with him here in Madrid, and I must say that on all fronts, he is great on and off the court."
Quoted by Spanish media, Djokovic said of Alcaraz: "I love watching him play, like many other players on tour. I praise his game without a doubt. It's fantastic for our sport, without a doubt.
"I think it's fantastic that we have a young player who is doing so well and who is breathing new life into the world of tennis."
Alcaraz expressed personal delight after defeating clay-court great and compatriot Nadal, battling back from an injury worry in the second set.
"It means a lot to me. All the hard work I put in every day has paid off," he said in the aftermath of his victory. "To beat Rafa, the best player in history on clay, it means a lot.
"The fall in the second set affected me a lot. When I lost the set I went to the bathroom and thought I would be able to come back to do my best and try everything.
"I wanted to fight until the last ball and that was the key."
Serbian superstar Djokovic scraped past Stefanos Tsitsipas in their semi-final on Saturday, snatching a 6-2 3-6 7-6 (7-4) victory.
Now 19-year-old Danish player Rune awaits the 21-time grand slam winner in Sunday's title match, a clash of generations that is full of promise.
It will be a record 56th Masters 1000 final for Djokovic, and a first for Rune, who will climb to 10th in the world should he win.
Rune is already assured of at least 12th position on the ATP list, a career-high, after knocking out four top-10 players this week: Hubert Hurkacz, Andrey Rublev, Carlos Alcaraz – who retired when trailing in their quarter-final – and Felix Auger-Aliassime, who he beat 6-4 6-2 on Saturday.
In his entire young career before this week, Rune had only beaten four players from the top 10, so this week marks a significant step, no matter how the final goes.
"No doubt that he's the future of the sport, along with Alcaraz and some other guys," Djokovic said. "Hopefully I can suspend his first title Masters 1000 event. We get along really well, good friends off the court.
"Of course on the court, we're competitors. I played him only once, at the last US Open, a good battle, four sets. He has improved a lot, no doubt. He physically is a very fit guy. He's young, so not much to lose. Just swinging through the ball.
"He kind of reminds me of myself, solid backhand and very good defence and just competitive, every point leaving his heart and his legs out there on the court. It's nice to see that. I think he's very good for our sport in general."
Djokovic said it was reassuring to fend off Tsitsipas, who had led by a break in the deciding tie-break.
"It means a lot mentally, emotionally for me, more than anything," said Djokovic. "I need to also make a statement that I'm still there with the young guys, that I'm able to compete with them and win such tight matches."
Six-time champion Djokovic has now reached an eighth final at this tournament, getting to the title match three times more than anyone else, with Boris Becker next on the list with five appearances.
Last month, the world number one and 20-time grand slam winner was deported from Australia on the eve of the Australian Open after his entry visa to the country was cancelled due to him not being vaccinated against coronavirus.
Djokovic believed he was still eligible to enter the country and compete after testing positive for coronavirus in December and making a full recovery.
The Serbian was subsequently sent home as he lost the legal battle that dominated much of the sports news agenda during the early weeks of 2022.
Djokovic is set to make his return to the court at the Dubai Duty Free Tennis Championships later this month, with vaccination not a requirement.
But it is at Indian Wells, where the five-time champion has been announced as a competitor, prompting curiosity about whether more legal battles await or if Djokovic has since been jabbed.
An Indian Wells statement read: "With health and safety as the tournament's top priority, the BNP Paribas Open will require valid proof of full vaccination to enter the Indian Wells Tennis Garden for the tournament.
"For the second consecutive year, the BNP Paribas Open has partnered with CLEAR, the secure identity company, to facilitate the implementation of the venue's mandatory vaccination policy ahead of the 2022 tournament.
"The guidelines for the players are governed by the protocols established by their respective governing bodies, the WTA and ATP, as well as any restrictions established by the United States of America in regard to the vaccination status of international travellers entering the country."
Images of Djokovic do not appear any of the tournament's build-up social media posts nor the website's promotional announcement, while his entry-list inclusion is little more than a footnote – but, crucially, it does include him.
The statement continued: "A power-packed line-up of ATP top-10 players will join [Rafael] Nadal in looking to put together a breakthrough performance in Tennis paradise.
"2021 US Open champion and 2022 Australian Open finalist Daniil Medvedev (world no. 2), 2021 ATP Finals winner Alexander Zverev (world no. 3), and 2021 French Open finalist Stefanos Tsitsipas (world no. 4) will each be in search of their maiden title in the desert.
"Reigning BNP Paribas Open champion Cameron Norrie (world no. 13) will look to replicate his extraordinary 2021 title run, in which he won his first Masters 1000 crown.
"World no. 1 and five-time Indian Wells champion Novak Djokovic is also on the tournament entry list."
Prior to this week's Masters 1000 event, Djokovic had not played since going down 6-4 6-4 6-4 to world number two Medvedev at Flushing Meadows in September.
That defeat ended Djokovic's hopes of sealing a calendar Grand Slam, but he was in fine form this week as he regained the title he last won in 2019, having not played in the competition last year.
Defending champion Medvedev started the final brilliantly, but Djokovic rallied to win 4-6 6-3 6-3, claiming a record-setting 37th Masters title in the process.
And the world number one explained how he learned from the mistakes he made in New York to prevail this time around, taking his head-to-head record with Medvedev to 6-4 in the process.
"I went back and reviewed the final of the US Open to see what I did wrong and what I did right," Djokovic told the Tennis Channel.
"I tried to read the patterns of his serve and the ball toss, maybe. I tried to look for the small details, because it was a match of small margins."
Reflecting on the showdown in Paris, Djokovic added: "He started better, broke my serve in the first game and I came back. He served the first set out pretty comfortably, but I felt as if I was there.
"I thought it was only a matter of time when I was going to read his serve better and start to make some plays.
"You can't go through him. You have to find a way to play with controlled aggression, play the right shots at the right time and make him come in. It's variety that wins matches against him. We both suffered on the court and there was a lot of gruelling rallies."
Djokovic, who had already secured a record seventh year-end number one, has won 49 matches in 2021, losing on just six occasions.
World number one Djokovic, playing in his first tournament since winning a ninth Australian Open in February, suffered his first defeat of 2021 on Thursday.
Evans, who had never before reached the last eight of a Masters 1000 tournament, won 6-4 7-5 with a performance that belied his relative lack of success on clay.
The 30-year-old Briton will now meet David Goffin, who surprised fifth seed Alexander Zverev 6-4 7-6 (9-7).
"To be honest, this has been probably one of the worst matches and performances from my side I can recall in the last years," said Djokovic. "I don't want to take anything away from his win, but from my side, I just felt awful on the court overall. Just nothing worked. It's one of those days."
Saying he felt "completely the opposite" to Wednesday's win over Jannik Sinner, Djokovic added: "Just was obviously very, very windy, tough to play in these kinds of conditions against a guy like Evans who makes you move. He's very unpredictable with his shots. He dismantled my game."
Eleven-time Monte Carlo champion Nadal had no such problems in his match as he dismissed Grigor Dimitrov 6-1 6-1 in 55 minutes.
Nadal, who boasts a 14-1 career record against the Bulgarian, did not face a break point in either set against his off-colour opponent.
Dimitrov started the match with three double faults in his opening service game and was 4-0 down in each set.
"[I am] sorry for him. He played a bad match. That is the truth," said Spaniard Nadal. "He made a lot of mistakes. I was there. I was doing the right thing, but it is true that today was more his fault than my good tennis."
Nadal will face Andrey Rublev after the Russian battled past Roberto Bautista-Agut 7-6 (7-2) 5-7 6-3.
Stefanos Tsitsipas, who beat Cristian Garin 6-3 6-4, will face Alejandro Davidovich Fokina next, while Fabio Fognini's straight-sets win over Filip Krajinovic set up a meeting with Casper Ruud.
The Serbian great is looking to get back to title-winning ways in his first tournament since September, when his hopes of a calendar Grand Slam were snuffed out by Daniil Medvedev in the US Open final.
He was pushed all the way to a deciding set tie-break by world number 10 Hurkacz, the player who beat Roger Federer at Wimbledon amid his breakout year.
But Djokovic had just enough in the tank to complete a 3-6 6-0 7-6 (7-5) semi-final victory, thumping his chest in relief and exhilaration as he got across the winning line.
On Sunday, he will bid to set another record by moving ahead of Rafael Nadal to reach 37 titles in Masters 1000 tournaments.
Saturday's success guarantees Djokovic will end the season on top of the ATP rankings for a record-breaking seventh time – Pete Sampras drops to second on the list with six years at the top.
Hurkacz broke serve in the eighth game of the first set and closed it out, only to surrender meekly in the second.
Djokovic broke to lead 3-1 in the decider, but a spirited Hurkacz recovered the break with a booming forehand into Djokovic's backhand corner in the seventh game.
The Polish player staved off a match point when serving at 5-4, getting somewhat lucky when a Djokovic passing shot landed just wide.
A tense tie-break swung Djokovic's way when Hurkacz lashed a forehand into the net at 5-5, and a backhand volley from the Miami Masters champion landed just wide on match point.
In the title match, Djokovic will tackle the winner of the second semi-final between Medvedev versus Alexander Zverev.
Victory in Paris would see Djokovic – competing for the first time since September's loss to Daniil Medvedev in the Flushing Meadows final – clinch the year-end number one ranking for a record seventh time.
Djokovic looked to be on course for a routine victory to start his campaign after comfortably taking the first set against Marton Fucsovics in their second-round contest on Tuesday.
However, the top seed's Hungarian opponent fought back to force a decider, hitting 13 winners to seven unforced errors in the second set.
But Djokovic – a record five-time Paris Masters champion – ensured a remarkable turnaround was not forthcoming, breaking Fucsovics twice in the third and, after letting one match point slip, clinching his second to secure victory.
Felix fights back
Ranked 12th in the ATP Race to Turin, Felix Auger-Aliassime needs to lift the trophy in Paris and hope Casper Ruud and Jannik Sinner do not reach the latter stages to make it to the ATP Finals.
Auger-Aliassime risked falling at the first hurdle on Tuesday as the ninth seed was forced to fight back to defeat Gianluca Mager 4-6 6-4 6-1.
"I had difficulty with my pace at the beginning of the match," said Auger-Aliassime. "I didn't hit enough first serves so I had a bit of pressure on my second serve.
"So I could have served better in the first set. I [had] a poor game at four-all and I got broken, but even before that there were moments at 30-all it was a bit hot and a bit tight. I think I relaxed. I found a better pace at the beginning of the second set, and it went even better as the match went forward."
He will next face Dominik Koepfer in the second round following the German's stunning win over Andy Murray on Monday.
Alcaraz sets up Sinner clash
Sinner will have an extremely testing second-round clash after Carlos Alcaraz came from behind to see off wild card Pierre Hugues-Herbert.
Alcaraz let slip a 4-2 lead in the first set to lose that on a tie-break but won six straight points in a second-set breaker before eventually battling to a 6-7 (4-7) 7-6 (7-2) 7-5 win in two hours, 53 minutes.
"It's not easy to play against a home player," Alcaraz said. "I think we played a good level and it was a great match, so I am happy to win. He has a great serve, so I had to return better and remain focus. I think that was the key. I am playing at a good level and I want to finish the year strong."
Diego Schwartzman – the 11th seed – needed three sets to see off John Millman, 15th seed Gael Monfils reversed a one-set deficit against Miomir Kecmanovic and 16th seed Grigor Dimitrov survived a three-setter with Richard Gasquet.
But one seed did fall on Tuesday, Roberto Bautista Agut (14) edged by James Duckworth in three sets.
