A comfortable 6-4 6-1 victory over Emil Ruusuvuori sent Ivashka into the second round, where world number six Tsitsipas awaits after receiving a bye.
Mallorca third seed Denis Shapovalov will face Benjamin Bonzi who benefited as Alejandro Tabilo retired while trailing 6-3 4-2 to the Frenchman.
Roberto Bautista Agut overcame Taro Daniel 6-4 7-6 (7-4) to advance, while Antoine Bellier defeated Federico Delbonis 6-3 7-6 (8-6) and Feliciano Lopez fell to a 7-6 (7-3) 7-6 (7-3) loss to Tallon Griekspoor.
De Minaur took an hour and 23 minutes to get past Cristian Garin 6-3 6-3 for a strong start in his bid to retain the trophy in Eastbourne.
The Australian will either face compatriot James Duckworth or Lorenzo Sonego, who he defeated in the final last year, in round two.
Fifth seed Reilly Opelka fell to a 6-3 6-1 defeat against tournament debutant Maxime Cressy, while Alexander Bublik was three points away from losing to Frances Tiafoe before rallying back to win 5-7 7-6 (7-4) 6-0.
Bublik will face John Millman next after the Australian overcame Sebastian Korda 6-3 7-6 (7-5), while top seed Cameron Norrie awaits Brandon Nakashima and Diego Schwartzman is next in line for Jack Draper.
Korda withdrew from Wimbledon after the defeat to Millman, the 21-year-old American saying on Twitter he was suffering with "terrible shin splints and beaten up feet" and needed a rest.
Wolf, the fifth seed at the United States' only clay court event on the ATP Tour calendar, needed just 75 minutes to send the Australian home early on the back of a rock-solid serving performance.
Thompson was not able to produce a single break point opportunity in the match, and Wolf left an exclamation point on the contest by winning the final five games to run away with the win.
Meanwhile, seventh seed Marcos Giron gave the American crowd another win to cheer for in his 6-0 6-2 demolition of Ecuador's Emilio Gomez.
The chance for the double-bagel was there for Giron after winning the first 11 games to race out to a 6-0 5-0 lead, but he blew four match points as Gomez showed no quit and secured a break to at least take the match over the 60-minute mark.
Eighth seed Tomas Martin Etcheverry prevailed 6-3 6-4 in his all-Argentine clash against Juan Manuel Cerundolo, taking a 3-2 lead in their overall head-to-head meetings after rising 21-year-old Cerundolo took the past two.
German qualifier Yannick Hanfmann booked a second-round matchup against second seed Tommy Paul after a hard-fought 6-4 3-6 6-2 triumph over Japan's Yosuke Watanuki, while Chile's Cristian Garin had little resistance in his 6-3 6-0 victory in a South American showdown against Bolivia's Hugo Dellien.
In the late window, Jack Sock failed to complete the United States clean sweep for the day as he fell 6-2 6-4 to the Czech Republic's Tomas Machac.
Karatsev showed astonishing defiance to beat the world number one 7-5 4-6 6-4 in the longest ATP Tour match of the year on Saturday.
The third seed from Russia saved 23 of the 28 break points he faced as his aggressive approach paid off, toppling the 18-time grand slam champion in a contest that lasted three hours and 25 minutes.
It was sweet revenge for Karatsev, who was beaten by the legendary Serbian at the semi-final stage of the Australian Open two months ago.
Djokovic had won 11 matches in a row in his homeland, but bowed out despite being 2-0 up in the first two sets as a solitary break in the decider ended his run.
Karatsev, the world number 28, said: "It was a long, tough match [against a] tough opponent.
"You have to put [in] like 200 per cent to beat this guy, it's like playing against a wall. And he also made some good shots.
"He doesn't give you any free points. He always makes you play and you have to be always there because once you miss a couple of shots, he just takes it very quickly. That’s how I lost the second set."
Berrettini secured his place in the final with a 6-1 6-7 (5-7) 6-0 victory over lucky loser Taro Daniel.
Second seed Berrettini only lost six points in the last set after Daniel came from a break down in the second before winning a tie-break to take the second semi-final the distance.
Heading into Sunday's final, Karatsev and Berrettini have never previously faced each other on the ATP Tour.
Three-time grand slam champion Murray had rolled back the years to reach his first ATP Tour championship match since beating Stan Wawrinka in Antwerp back in October 2019.
There was to be no 47th ATP Tour singles title for the Briton at Ken Rosewall Arena, though, as Karatsev won 6-3 6-3 to ensure he will start the Australian Open next week with a spring in his step.
The world number 20 from Russia was a surprise semi-finalist in the first grand slam of the year at Melbourne Park last year and looks capable of making his presence felt again.
Karatsev struck 27 winners to 13 from the racket of former world number one Murray, who was unable to break the Vladikavkaz native's serve.
Murray failed to hold in the first game of the final and the opening set was over when he was broken for a second time.
Karatsev surged into a 3-0 lead in the second set and fended off five break points before finally holding to take a 4-1 lead, then went on to serve it out as he secured a third ATP Tour singles title, having been triumphant in Moscow and Dubai last year.
Murray will take great heart from the strides he has made this week and three years after fearing he may be force to retire at the Australian Open, the 34-year-old will face Nikoloz Basilashvili in the first round of the 2022 tournament next week.
Karatsev will do battle with Spaniard Jaume Munar for a place in the second round at Melbourne Park.
Having defeated Jo-Wilfried Tsonga in the second round, Kecmanovic – who enjoyed a run to the semis at the Next Gen ATP Finals last year – cruised past Marton Fucsovics in 56 minutes on Thursday.
Kecmanovic's 6-2 6-0 triumph puts him into the last four, though he will not find out his fellow semi-finalists until Friday after the rain arrived.
Kecmanovic will face either Andrey Rublev or Pierre-Hugues Herbert, while Corentin Moutet faces Fernando Verdasco and Stan Wawrinka goes up against Aljaz Bedene.
Herbert and Rublev were locked at 1-1 in the opening set when rain stopped play.
The world number 47 came agonisingly close to a maiden tour-level trophy in 2019, only to fall short against Lorenzo Sonego at the Antalya Open.
However, he made sure to grasp his opportunity this time around, and was in clinical form to dispatch three of four break points conceded by his German opponent.
"Last year sucked when I couldn't win the final," Kecmanovic said post-match. "I definitely have a lot more experience since then and it means everything to be able to win a title.
“[The last game] wasn't pretty, it was definitely difficult. I just tried not to think that it was potentially the last game and I just tried to hit my serves at the right spot. Thankfully, I was able to do that."
Kecmanovic defeated Kei Nishikori, Jordan Thompson, Federico Delbonis and Marc-Andrea Huesler en route to his triumph in Austria, and he becomes the fourth player to win his first ATP Tour title in 2020, following on from Ugo Humbert, Casper Ruud and Thiago Seyboth Wild.
Kokkinakis was beaten by Gael Monfils in the semi-final of the Adelaide International 1 last weekend, but the 25-year-old got his hands on the trophy on Saturday after a 6-7 (6-8) 7-6 (7-5) 6-3 win.
The Australian saved two match points in a semi-final defeat of Marin Cilic and showed his fight again to deny Rinderknech a first title.
Kokkinakis has had a tough time with injuries since rising to a career-high ranking 69 as a teenager in 2015, but he has shown what he is capable of early in the season ahead of the Australian Open.
There were no break point in the first two sets, but Frenchman Rinderknech failed to hold twice in the decider on a special day for Kokkinakis.
Kokkinakis said: "I wouldn't want to win my first title anywhere else. To my family, friends and coaches, what a ride it's been. You have seen me at my lowest lows and now the highest high. It's been a serious journey. For now, I am so happy.
"I've been playing and practising on this court since I was eight or nine years old, coming here before school every day. I love this court so much."
Kokkinakis will play qualifier Yannick Hanfmann in the first round of his home grand slam next week, while Rinderknech takes on Alexei Popyrin at Melbourne Park.
Korda became the first American man to be crowned a champion on clay in Europe for 11 years, beating the Italian wildcard 6-2 6-4 in Parma.
The unseeded 20-year-old son of former world number two Petr Korda did not drop a set this week and will head to the French Open with his confidence sky-high.
Korda won 82 per cent of points behind his first serve and broke three times to get the better of Cecchinato at the President Tennis Club.
The Florida native took just an hour and 15 minutes to become the first American man since Sam Querrey in Belgrade back in 2010 to win a title in Europe on this surface.
His victory ensured the Kordas are the third father-son duo to win ATP Tour-level singles titles in the Open Era, emulating Ramanathan Krishnan and Ramesh Krishnan, and Phil Dent and Taylor Dent.
World number 63 Korda will face Spaniard Pedro Martinez in the first round at Roland Garros next week.
Korda was playing his first indoor match since the decider of the Next Gen ATP Finals last November, and Hugo Gaston represented a tough opening test.
But the American prevailed in straight sets against the home favourite, winning 6-3 7-6 (7-2) after defending set points in the second set and blowing his opponent away in the subsequent tie-break.
Another tricky opponent awaits, with number three seed Lorenzo Musetti up next in the second round.
Musetti's Italian compatriot Sonego also succeeded in Monday's only other main-draw match, beating sixth seed Aslan Karatsev 7-5 6-3 to set up a last-16 clash with either Gilles Simon or David Goffin.
In the qualifying section, three-time grand slam champion Wawrinka beat Zsombor Piros 6-7 (4-7) 6-2 6-0 to reach the first round, where Joao Sousa awaits.
The winner of that match will face top seed Daniil Medvedev in the last 16.
American Kovacevic was only playing in the first round as a lucky loser in Seoul after he was beaten in the final round of qualifying, but he grasped his chance by winning 6-4 6-4.
The 24-year-old served 14 aces and broke the world number 32 three times to set up a second-round meeting with Christopher O'Connell or Tseng Chun-hsin.
Radu Albot got the better of Hiroki Moriya in his first appearance in Seoul, while Jaume Munar progressed when Yosuke Watanuki retired early in their match due to an ankle injury.
Kaichi Uchida came out on top in the final match of the day, consigning Hong Seong-chan to a 6-4 6-2 defeat.
Krajinovic was the only seeded player in action and he was dominant against home hope Lazarov, who is ranked 462 in the world.
The Serbian swept the first set without conceding a break point and finished the job by claiming the last four games in the second despite Lazarov putting up more of a fight.
Elsewhere, Krajinovic's compatriot Miomir Kecmanovic crashed out to Italian Gianluca Mager, who fired down 11 aces and forced 10 break-point opportunities to earn an impressive 7-6 (7-3) 6-3 win.
Australian James Duckworth, meanwhile, had to launch a comeback before ultimately prevailing 3-6 6-4 6-4 against Finland's Emil Ruusuvuori to book a round two match with Benoit Paire.
The number one seed and defending champion Jannik Sinner will begin his campaign on Thursday with a last-16 contest against Egor Gerasimov.
Second seed Gael Monfils will play Ilya Ivashka, who defeated Pablo Andujar in straight sets, with the winner to face Mager, who is the first man in the quarter-finals.
Alex de Minaur will also be in action against American Marcos Giron.
A memorable week for Krajinovic continued as he saw off fellow Serbian Laslo Djere 6-4 6-2 in his semi-final.
Sixth seed Krajinovic defeated Stefanos Tsitsipas in the quarter-finals and ensured he followed up on that surprise victory with a dominant display against Djere on Saturday.
The victor committed only seven unforced errors in the match, while conceding just two break points in the contest.
Second seed Carreno Busta has not dropped a set all week and kept that run going with a 7-6 (7-2) 6-3 win over Federico Delbonis.
Carreno Busta needed just under two hours to see off a battling Delbonis, with neither player offering up a single break point in a first set that went the distance.
The Spaniard won five straight points to take the tie-break and continued that momentum into the second set when he broke Delbonis twice.
Neither Carreno Busta nor Krajinovic has ever won a tournament at ATP 500 level or above.
Carreno Busta has five career titles, but all of those are at ATP 250 level, losing to Dominic Thiem in his only showpiece appearance at this level at the Rio Open back in 2017.
Krajinovic, meanwhile, has lost all three of the career finals he has reached.
"I enjoy playing here, I feel comfortable here," Carreno Busta said. "It is my most important match this year on Sunday - I need to be really focused until the end.
"[Delbonis] is a really tough player and my level was very good. I probably played better in the second set, but I continued fighting all the time."
At the Nordea Open in Bastad, Sweden, top seed Casper Ruud was comfortable as he defeated Roberto Carballes Baena 6-1 6-4 to earn a place in the final.
Ruud needed just 79 minutes to do the job, breaking Carballes Baena on five occasions.
He has only played two matches – both comfortable wins – to reach the final after a walkover against Henri Laaksonen in the quarters.
Rising star Ruud will bid for his second ATP title of the year and the third of his career against Federico Coria on Sunday.
Coria also had a comfortable last-four tie, seeing off Germany's Yannick Hanfmann 6-2 6 -1, with the win meaning the 29-year-old reached his maiden career tour final.
"I am very happy - it is my first final," said world number 77 Coria, who beat second seed Cristian Garin in the last eight.
"I played the best tennis of my life in this match. It is amazing here in Bastad, it is beautiful."
The South Korean came out on top in the battle of the unseeded first-time finalists on Sunday, winning 7-6 (8-6) 6-3 in Nur-Sultan.
Kwon won 86 per cent of points behind his first serve and came from behind in both sets to be crowned champion.
Australian Duckworth failed to convert three set points in a tie-break and Kwon made him pay, grasping his first opportunity to go a set up.
Kwon was broken in the first game of the second set, but the battling world number 82 hit straight back to draw level.
Duckworth, who had not dropped a set en route to the final, was broken again to trail 4-2 and he was unable to find a way back as the 23-year-old Kwon celebrated his finest hour.
Raonic advanced to the Australian Open quarters before falling to eventual champion Novak Djokovic last month, however, the Canadian was stunned in New York on Wednesday.
Kwon weathered 33 aces from Raonic as the South Korean prevailed after two hours, 25 minutes at the ATP 250 tournament midweek.
"I'm really happy to win a tough match against Raonic," Kwon during his on-court interview. "He played well. It was a great match."
Next up for Kwon is either eighth seed Kyle Edmund or Dominik Koepfer.
While Raonic bowed out, fellow seeds Ugo Humbert and Miomir Kecmanovic progressed from the last 16.
French fourth seed Humbert eased past Marcos Giron 6-1 6-0, sixth-seeded Serb Kecmanovic defeated Paolo Lorenzi 6-3 6-3, while Andreas Seppi saw off Steve Johnson 7-6 (7-4) 6-3.
At the Argentina Open, fourth seed Coric was sent packing by Thiago Monteiro – who won 6-4 7-6 (8-6) in Buenos Aires.
Despite letting a match point slip at 6-5 in the second-set tie-break, Monteiro moved through to his first ATP Tour-level quarter-final since 2018.
Pedro Sousa awaits after the lucky loser accounted for Jozef Kovalik 7-6 (7-3) 7-6 (7-5) on the clay courts.
Dusan Lajovic – the third seed – outlasted qualifier Pedro Martinez 7-6 (8-6) 7-6 (8-6) to set up a quarter-final with eighth seed Casper Ruud, who dismantled Roberto Carballes Baena 6-1 6-0.
Briton Edmund – contesting his first ATP Tour final since 2018 – claimed a 7-5 6-1 victory in New York.
The eighth-seeded Edmund prevailed over Italian opponent Seppi after one hour, 21 minutes for his second ATP crown.
Edmund, who reached the 2018 Australian Open semi-finals, used his serve to see off Seppi on the American hard courts at the 250 tournament.
The South Africa-born Edmund won 31 of his 33 first serve points and did not face a break point throughout the match.
Edmund broke three times en route to his first trophy since winning the 2018 European Open in Belgium.
It was the first time Kyrgios had played on clay since his infamous meltdown at the Rome Masters in 2019, where he threw a chair across the court and walked off, handing Casper Ruud a win by default.
After a meandering first set, the Australian world number 94 sparked into life when he saved the first of two break points with a second serve ace in the third game of the second. From there, Kyrgios opened up his shoulders and became more assertive from the baseline, as well as serving 18 aces in the closing two sets.
While again admitting clay is not his favourite surface, the 26-year-old was nevertheless pleased by the manner of the win against McDonald.
"He [McDonald] beat me in Washington where I used to play pretty well, and he's a tricky one because he doesn't make too many errors, and clay's obviously not my preferred surface," he said post-match.
"I just served really well, and just started playing more aggressive and found another gear. I would slip and slide a little bit, but my game actually suits the clay quite well."
While US seventh seed Tommy Paul secured a walkover 6-7 (4-6) 7-6 (7-5) 3-2 win against Peter Gojowczyk, Chilean fifth seed and defending champion Cristian Garin also came from a set down to beat Jack Sock 4-6 6-3 7-5.
American sixth seed Frances Tiafoe faced relatively simpler work, defeating unseeded countryman Marcos Giron in straight sets 6-4 6-4.
Two all-American matches also opened play in Houston on Tuesday, with JJ Wolf securing a 6-4 6-4 win over eighth seed Jenson Brooksby in the first, and Steve Johnson defeating Denis Kudla 6-3 4-6 6-4.
Kyrgios' replacement in Adrian Mannarino eventually defeated Gojowczyk 6-3 7-6 (9-7), but the Wimbledon finalist's withdrawal due to injury overshadowed the match.
After receiving a wild card for the Cincinnati Masters, the 2016 champion in Atlanta was expected to make a deep run to kick off his hard-court season.
Coming out to apologise to the crowd before Gojowczyk and Mannarino took to the court, Kyrgios expressed his sadness at the withdrawal, in the hope he could still play in the doubles draw with fellow Australian Thanasi Kokkinakis.
"I'm extremely shattered that I'm not able to compete tonight," he said pre-match. "I've won this tournament once, and you know, I'm playing some of the best tennis of my career.
"All I wanted to do was come out here and give you guys a show, to see what I was capable of. I'm unable to give out my best performance today, and I'm just extremely sorry.
"I'm going to keep my hopes up and maybe be able to continue doubles with Thanasi this week. I hope you'll all not be too hard on me."
Kokkinakis just has the doubles to attend to now after Andres Martin's 6-3 6-2 win, while Ilya Ivashka progressed with a 6-0 3-6 6-3 win over Quentin Halys.
James Duckworth was the lone Australian to advance on Tuesday, beating Dominik Koepfer 6-1 6-7 (5-7) 6-3.
Jenson Brooksby made an encouraging Atlanta Open debut earlier in the day, eliminating Benoit Paire 6-3 6-1 to reach the second round.
Countryman and fifth seed Tommy Paul breezed past wild card Jack Sock 6-1 6-1, while Ben Shelton and Mackenzie McDonald also advanced.
Londero progressed to the last eight of the ATP 250 tournament thanks to a 6-3 6-3 win over Argentinian compatriot Pedro Cachin on Thursday.
Cordoba was the scene of Londero's breakthrough ATP Tour title last year, the Argentine player capping a fairytale week by overcoming countryman Guido Pella in three sets.
Next up for Londero on the red clay is Serbian fourth seed Laslo Djere, who beat Spanish qualifier Pedro Martinez 6-3 6-4.
"I was a little nervous and that's why I talked to myself a lot and that's how I got in the game. The way I have to activate [myself] is by encouraging myself a lot. If I keep quiet, that doesn't happen. It was a game with many nerves for me, and I am glad I won it in straight sets," Londero said.
"For me, it is more a motivation than a pressure to play in Cordoba and try to defend the title. If I had to defend the tournament elsewhere, without having the support of my family, my friends who can see me live, the truth is that I think it would be more difficult anywhere else. I have been having a good time."
Albert Ramos-Vinolas – the fifth seed – outlasted Pablo Andujar 6-3 6-7 (4-7) 6-4 to set up a clash with Schwartzman, who defeated Jaume Munar 6-1 7-5.
Cordoba was the scene of Londero's breakthrough ATP Tour title last year, the Argentinian capping a fairytale week by overcoming countryman Guido Pella in three sets.
Back on the red clay following a first-round loss at the Australian Open in January, eighth seed Londero defeated Italy's Marco Cecchinato 6-2 7-5.
Londero – playing the night session – did not face a break point and won 70 per cent of his first serves, much to the delight of the home crowd at the ATP 250 tournament.
Next up for Londero is fellow Argentine player Pedro Cachin, who crushed Hugo Dellien 6-1 6-1 in just 58 minutes.
Spanish fifth seed Ramos-Vinolas beat local qualifier Facundo Bagnis 6-4 7-6 (7-3), despite wasting a match point at 6-5 in the second set.
It will be an all-Spanish affair in the last 16 after Pablo Andujar accounted for Filip Horansky 6-2 6-2.
Elsewhere, Jaume Munar (6-4 6-3 against Leonardo Mayer), Andrej Martin (7-6 [7-5] 6-4 over Federico Coria), Pedro Martinez (4-6 6-3 6-4 against Federico Gaio) and Corentin Moutet (6-4 6-3 over Thiago Monteiro) also progressed to the next round.
The world number six, playing in his first tournament in five months due to injury, has now won at least one ATP Tour trophy in every season since 2004 onwards.
American qualifier Cressy more than held his own in a first set that went the distance, though Nadal's quality told as he prevailed 7-6 (8-6) 6-3 at Rod Laver Arena, where Nadal will be hoping to go deep in the season's first grand slam later this month.
Both men held in an entertaining opening set and Cressy led 6-5 in the tie-break, but he squandered his set point and Nadal hit back to grab a foothold on the match.
The 35-year-old, who won the tournament without dropping a single set, recovered from a break down in the second to add yet another trophy to his vast collection.
Nadal, who had not played since August before coming into this tournament and had COVID-19 last month, had not previously captured a title in Australia since 2009 when landing his only Australian Open triumph to date by beating Roger Federer.
And the Spaniard looks in good shape heading into the Australian Open, which may not feature defending champion Novak Djokovic, who is awaiting the outcome of a hearing to determine whether he will be able to compete in Melbourne.
"I feel privileged and a very lucky guy to be here again," Nadal said in his on-court interview.
"I am coming back from some challenging moments in terms of injuries, so I can't be happier. It means a lot to be back and with a trophy in my hands.
"This court has always been very, very special for me. The Rod Laver Arena is very, very special for everyone and it is more special because of you guys. You guys are a great crowd and I can't thank you enough."
Elsewhere on Sunday, Gael Monfils also made a promising start to the 2022 season with a 6-4 6-4 victory over Karen Khachanov in the Adelaide International 1 final.
Khachanov battled past former US Open champion Marin Cilic in the semi-finals, but he fell short of clinching a first title in over three years.
Top seed Monfils held throughout the opening set and found a breakthrough in the 10th game, with the second set following an identical pattern.
The Frenchman did not drop a set all tournament on his way to winning a first trophy since February 2020 in Rotterdam.
