Top seed Nadal secured an opening-set bagel in just 30 minutes, but Nishikori hit back to force a decider before the 20-time grand slam champion prevailed 6-0 2-6 6-2.
Nishikori hit only three winners as he was blown away in the first set, but broke twice in the second to ensure Nadal was taken to three sets in back-to-back matches for the first time in this tournament – having overcome Ilya Ivashka in the second round.
The world number three saved three break points from 0-40 down in the final set and Nishikori saw another two come and go, with a more clinical Nadal breaking twice to advance.
Nadal will now face unseeded Brit Cameron Norrie, who also won the first set 6-0 and was 5-3 down to David Goffin in the second when the Belgian retired due to a leg injury.
Newly-crowned Monte Carlo Masters champion Tsitsipas defeated Alex de Minaur 7-5 6-3, stretching his straight-sets winning streak to seven matches.
Next up for the second seed is a meeting with Felix Auger-Aliassime, who beat fellow Canadian Denis Shapovalov 6-2 6-3, while Jannik Sinner beat Roberto Bautista Agut 7-6 (11-9) 6-2.
Andrey Rublev, Diego Schwartzman and Pablo Carreno Busta also made it through.
Two seeds fell in the Serbia Open, with Federico Delbonis taking out Dusan Lajovic 6-3 2-6 6-4 and Taro Daniel defeating John Millman 3-6 6-2 6-3.
Gianluca Mager moved into the quarter-finals at the expense of Alexei Popyrin and Aslan Karatsev battled past Aljaz Bedene 6-3 4-6 7-6 (7-5) in Belgrade.
A two-time champion of the event, top seed Nadal cruised past Spanish compatriot Pablo Andujar 6-3 6-2 on Tuesday.
In competitive action for the first time since the Australian Open, Nadal needed just 90 minutes to post his fourth victory in as many meetings with Andujar.
Zverev, the second seed at the ATP 500 tournament, survived an early battle before getting past Jason Jung 7-6 (8-6) 6-1.
Last year's runner-up, Zverev served 12 aces and broke four times in his victory.
Kyrgios beat Zverev in the final in 2019, but the Australian lasted just 31 minutes in the first round.
Ugo Humbert took the first set 6-3 when Kyrgios retired due to a wrist injury, the 24-year-old receiving some boos as he left the court.
Kyrgios was the only seed to fall as Felix Auger-Aliassime, John Isner, Grigor Dimitrov and Dusan Lajovic advanced at the hard-court tournament.
Taylor Fritz, Pedro Martinez and Kwon Soon-woo were also among the winners.
At the Chile Open in Santiago, seeds Juan Ignacio Londero, Federico Delbonis and Thiago Monteiro all got through their first-round matches.
Nadal – playing his first competitive tournament since the Australian Open – produced some highlight moments as he saw off Miomir Kecmanovic 6-2 7-5 in Acapulco on Wednesday.
A two-time winner of the ATP 500 event, world number two Nadal was a class above against his Serbian opponent to stay on course for the title.
After his powerful display, the 19-time grand slam champion will face Kwon Soon-woo for a spot in the semi-finals after the South African beat eighth seed Dusan Lajovic 7-6 (7-2) 6-0.
Australian Open semi-finalist Zverev was bundled out of the tournament by American qualifier Tommy Paul 6-3 6-4.
Zverev dropped his opening service game and it was a sign of things to come for the German star as Paul capitalised to eventually claim the biggest win of his career.
Next up for 22-year-old Paul is fifth seed John Isner, who downed fellow American Marcos Giron 6-3 7-6 (7-4).
Grigor Dimitrov saved two match points as he prevailed 6-7 (8-10) 6-2 7-6 (7-2) against Adrian Mannarino in a thriller.
Mannarino erased Dimitrov's 4-1 lead in the final set to earn a pair of match points but the Bulgarian rallied to set up a showdown with third seed Stan Wawrinka, who eased past Pedro Martinez 6-4 6-4.
Elsewhere, fourth seed Felix Auger-Aliassime was surprised 6-4 6-4 by Kyle Edmund and Taylor Fritz topped Ugo Humbert 6-4 6-1.
At the Chile Open in Santiago, seeds Casper Ruud, Hugo Dellien and Federico Delbonis all moved through to the quarters but Pablo Cuevas fell to qualifier Renzo Olivo.
Nadal was in devastating form as the 19-time grand slam champion dismantled Kwon 6-2 6-1 at the ATP 500 tournament in Acapulco on Thursday.
After crushing Miomir Kecmanovic in the last 16, Nadal continued his ruthless path through the draw at the expense of the rising South Korean in one hour, 31 minutes.
Nadal – eyeing his third Acapulco title – hit 25 winners, 11 unforced errors and saved all eight break points he faced to set up a semi-final showdown with Grigor Dimitrov.
Bulgarian Dimitrov snapped a five-match losing streak against three-time major champion Stan Wawrinka by defeating the third seed 6-4 6-4.
Dimitrov – the 2014 Mexican Open champion – had not beaten Wawrinka since 2016 but the former world number three ended his drought in one hour, 25 minutes.
"I've played quite a few times against Stan and we've practised together so many times. Between us, it's mainly a mental battle," Dimitrov said. "I had lost the past five times against him, but those losses have inspired me. Those losses helped me. Even though it hurts saying it, I'm admitting it. I wanted to stand tall tonight."
John Isner – the fifth seed – booked his spot in the semis for the second successive year with a 7-6 (7-3) 3-6 6-2 win over fellow American Tommy Paul.
Isner fired down 22 aces to set up a clash against countryman Taylor Fritz, who topped Kyle Edmund 6-4 6-3.
At the Chile Open, in-form top seed Cristian Garin extended his winning streak en route to the quarter-finals in Santiago.
Garin – the Cordoba and Rio Open champion – celebrated his 10th consecutive victory by downing Alejandro Davidovich Fokina 6-2 0-6 7-6 (7-4) at the ATP 250 event.
Fellow seeds Albert Ramos-Vinolas and Thiago Monteiro also progressed but fifth seed Juan Ignacio Londero was upstaged by wildcard Thiago Seyboth Wild 7-6 (9-7) 6-4.
The world number three was pulled out of this month's tournament in Acapulco following an outburst where he hit the umpire's chair with his racquet in a tirade following a doubles defeat.
The ATP subsequently barred him from competition for a second-round singles clash, with several leading players, including Novak Djokovic, condemning the German's actions.
Speaking ahead of his own quarter-final this week, Nadal - who won a record-breaking 21st Grand Slam in at the Australian Open last month - stated he hoped the 24-year-old and other young players would learn that such behaviour is not acceptable.
"It's unfortunate, without a doubt," the Spaniard said. "I feel sorry for him as I have a good relationship with Alexander.
"In the end, he deserves the sanction because you can't act in this way.
"I think Sascha is aware of that and I hope this will serve as a lesson for him and for other young players who sometimes lose control on the court.
"I am not going to enter into what is or is not fair in terms of sanction," Nadal said. "But in the end you have to stop that type of attitude from becoming fashionable."
Zverev had been due to face Peter Gojowczyk in a singles encounter before he exploded at the end of his match with partner Marcelo Melo against Lloyd Glasspool and Harri Heliovaara.
Following an over-ruled decision from the umpire that handed the latter pair match point in a super tie-break, the duo decided the game with an ace the very next serve.
That led to Zverev smashing his racquet against the umpire's chair on multiple occasions in quick succession, punctured by a foul-mouthed tirade.
The Tokyo 2020 champion subsequently apologised for his behaviour. The Mexico Open continues until February 26.
In his first match since a record 21st grand slam title in Australia, Nadal was a comfortable 6-3 6-2 winner over Denis Kudla, dropping only four points on serve.
Nadal is now 11-0 for the season, equalling the start he made in 2014, when his winning run was ended by Stan Wawrinka in the Australian Open final.
"I think I started playing well, a good victory in straight sets. That's always very positive for the confidence," said Nadal. "I think I played a very solid match for the first day.
"Of course, there are a couple of things that I can do better, but in general terms, I played well, so I can't complain at all."
Daniil Medvedev, who had also not played since the final in Melbourne, came through a tougher contest against Benoit Paire 6-3 6-4 in his opening match in Acapulco.
Medvedev held a two-set lead and looked in control before Nadal came roaring back to claim the Australian Open title, but the Russian could claim a landmark achievement in his first tournament since that heartbreak.
Medvedev, who faces Pablo Andujar next, will become world number one if he wins in Mexico, regardless of Novak Djokovic's performances in Dubai.
"It's always not easy to come back after some rest and some time off competition," he said. "I felt like my sensations were not at the top today, but I managed to fight until the end against a very tough opponent, and I'm happy that I managed to win."
Stefanos Tsitsipas racked up the 200th win of his career, holding off Laslo Djere to win two tie-breaks. He will now face J.J. Wolf, who surprised Lorenzo Sonego by fighting back from a set down to win 3-6 7-6 (9-7) 6-2.
Cameron Norrie was a straight-sets winner over Daniel Altmaier, while Yoshihito Nishioka battled through against veteran Feliciano Lopez.
Tommy Paul progressed after Matteo Berrettini retired when the American was poised to tie the match at one set all. John Millman also had to call an early halt to his match with Marcos Giron after a freak accident on court in which the Australian accidentally hit a ball into his eye.
At the Chile Open, home favourite Alejandro Tabilo beat Renzo Olivo in straight sets, while fifth seed Federico Coria was earlier knocked out by Yannick Hanfmann.
Miomir Kecmanovic defeated Marco Cecchinato, while there were also wins for seeds Sebastian Baez and Facundo Bagnis.
Top seed Nadal was too good for Dimitrov en route to his fourth Mexican Open decider, triumphing 6-3 6-2 in convincing fashion at the ATP 500 tournament on Friday.
Nadal won the event in 2005 and 2013 and the 19-time grand slam champion has the chance to claim a hat-trick of Acapulco titles after maintaining his relentless form.
"I'm very happy. A great victory against one of the best players in the world and a good friend," Nadal said. "I think I've increased my level during the match, so it's positive for me."
Spanish star Nadal recovered from 1-2 start, reeling off four consecutive games with some powerful baseline winners to seize control against seventh seed Dimitrov.
It was a similar theme in the second set as Dimitrov broke for a 2-0 lead but that was as good as it got for the Bulgarian – Nadal going on a six-game run to close out proceedings in one hour, 41 minutes.
Awaiting world number two Nadal in the final is Taylor Fritz after the American stunned fifth seed John Isner 2-6 7-5 6-3 in a stunning comeback.
"He's playing well. He has a great serve, fantastic shots from the baseline. It's going to be a tough one," Nadal said. "I know I'm going to have to be at my best and I hope to be ready for it."
At the Chile Open, second seed Casper Ruud defeated seventh seed Federico Delbonis 7-5 7-5 to book his spot in the semi-final.
Ruud – the first Norwegian to win an ATP Tour title in Buenos Aires – will next meet third seed Albert Ramos-Vinolas, who saw off Thiago Monteiro 6-4 6-4 in Santiago.
Top seed Cristian Garin was forced to retire due to a leg injury after losing the first set 7-6 (7-1) to Thiago Seyboth Wild, while Renzo Olivo upstaged Pablo Cuevas 3-6 7-6 (7-5) 7-5.
Nadal beat fellow Spaniard Pablo Carreno Busta 6-3 6-2 to stand on the brink of being crowned champion for a 12th time at the Real Club de Tenis Barcelona 1899.
The top seed won 77 per cent of points on his first serve and returned superbly in yet another sublime clay-court exhibition.
Nadal broke Carreno Busta in his compatriot's first service game and ominously charged into a 5-1 lead in imperious fashion on Pista Rafael Nadal.
Carreno Busta broke back to prolong the opening set, but the 20-time grand slam champion wrapped it up in 45 minutes before swiftly taking charge of the second.
The world number three breezed into a 4-0 advantage and did not face a solitary break point as he took just shy of an hour and a half to set up a showdown with Tsitsipas, who knocked him out of the Australian Open at the quarter-final stage in February.
Tsitsipas maintained his magnificent form with a 6-3 6-3 defeat of Jannik Sinner.
The in-form Greek won the Monte Carlo Masters last weekend and matched Andrey Rublev's ATP tour-leading total of 26 victories this season by steering past Sinner.
Second seed Tsitsipas has won all 17 sets he has played on clay this season, having saved all four break points that Sinner earned.
The world number two has been struggling with a lower back injury sustained prior to the Australian Open, which he exited in the quarter-finals at the hands of Stefanos Tsitsipas.
Nadal has not competed since, having subsequently pulled out of the ATP Cup and Rotterdam Open after being advised to give his back time to heal.
And the 20-time grand slam winner will delay his return for a little while longer after deciding to skip the upcoming ATP 500 event in Dubai.
"I would like to thank the @DDFTennis for the wild card invitation sent to me," Nadal posted on his Twitter page on Thursday.
"We seriously thought about coming to play, but I don't think I am ready to play yet. Once again thanks to the tournament's kind invitation and best of luck with the tournament."
The Spaniard added in a later tweet: "And special thanks to Tournament Director Salah Talak since I am aware of his efforts to ensure a smooth arrival to play Dubai during this unprecedented Coronavirus pandemic and difficult times for all."
Nadal won his only Dubai Tennis Championships title in 2006 with victory over Roger Federer – the competition's record eight-time winner – in the final.
Federer is scheduled to take part in this year's tournament after making his long-awaiting return from a 14-month injury lay-off at the Qatar Open this week.
Nadal continued his undefeated start to 2022 with his third title for the year after beating the British sixth seed 6-4 6-4 in Acapulco on Saturday.
He is now on a run of 15-0 this season, claiming his 91st ATP Tour crown along the way.
It was also Nadal's fourth Mexican Open title, having previously won in 2005, 2013 and 2020.
His recent win at the Australian Open put him clear of Novak Djokovic and Roger Federer on 21 grand slam titles, but he still sits behind Ivan Lendl (94), Federer (103) and Jimmy Connors (109) for ATP tournament victories.
After his win in Mexico, Nadal said he is not concerned about records as long as he is still playing, saying: "At the end of the day, I've always said that this kind of record needs to be measured once your career is over.
"Today the most important thing is that I have won a prestigious tournament."
The 35-year-old's incredible form is all the more impressive considering he was forced to miss last year's US Open to deal with a foot issue that troubled him all the way to the lead-up to January's Australian Open.
"It was complicated, and I ended up taking the victory. Looking back, a few weeks ago this would have looked impossible," he added.
"It's amazing how things can change in such a short span, from not being able to practice and now to be where I am today."
The Spanish great proved too good for Fritz 6-3 6-2 in just 74 minutes in the decider in Acapulco.
Nadal won the ATP 500 title for a third time and first since the event changed from clay to hard-court in 2014.
The 19-time grand slam champion did not drop a set at this year's tournament on his way to a first title of 2020.
Nadal only lost nine points on serve in his victory, while managing three breaks in a comfortable win over the American.
The 33-year-old grabbed a break in the eighth game of the first set before winning five straight in the second on his way to the title.
Only Jimmy Connors (109), Roger Federer (103) and Ivan Lendl (94) have won more ATP Tour titles than Nadal's 85 in the Open Era.
At the Chile Open in Santiago, Casper Ruud will face Thiago Seyboth Wild in the final.
The 22-time grand slam winner has not played since going out to Mackenzie McDonald in the second round of the Australian Open in January.
Nadal did not feature at tournaments in Indian Wells or Monte Carlo, and his latest withdrawal casts further doubt on his participation at the French Open, which begins at the end of May.
He wrote on Instagram on Friday: "Barcelona is a special tournament for me, because it's my adopted club and because playing at home is always a unique feeling.
"I'm still not prepared and therefore I'm still in my preparation process for the return to competition.
"Good luck to my friend [tournament director] David Ferrer and his whole team for this edition of the Godo that will surely be a success as always on all levels."
Nadal is a 12-time winner of the Barcelona Open, which he last won in 2021.
The 36-year-old recently dropped out of the world's top 10 men's rankings for the first time since 2005 due to his injury absence, and he currently sits in 15th place.
The world number two was scheduled to represent Spain in next week's tournament at Rotterdam Ahoy but has been replaced by Reilly Opelka of the United States.
Twenty-time grand slam winner Nadal has been struggling with a lower back injury and was also forced to pull out of Spain's ATP Cup ties this month.
The 34-year-old was cleared to take part in the Australian Open, where he did not drop a set before losing to Stefanos Tsitsipas in the quarter-finals.
However, Nadal has still not fully recovered from the issue and will now miss another event.
Organisers of the ATP 500 tournament confirmed the news on Thursday and Nadal later took to Twitter to explain the decision.
"It is with great sadness that I have to forfeit from Rotterdam," he said. "As most of the fans know, I suffered some back problems in Australia that started in Adelaide and continued during Melbourne.
"We found a temporary solution that allowed me to play without pain in the second week of the tournament. Once I got back to Spain I visited my doctor and together with my team they've advised not to play this upcoming week.
"I was really looking forward to coming back to Rotterdam and The Netherlands since it's been a while I played there this was the perfect year for my calendar.
"I hope to come back and play there soon. All the best to the tournament, always a top-class event."
World number three Daniil Medvedev will replace Nadal as the top seed in the Rotterdam tournament, which runs from March 1-7.
A 6-4 6-4 loss came against a player he once led 13-1 in their career head-to-head, a gap which has now closed to 13-4 after a hat-trick of wins for Spanish left-hander Verdasco.
Following victories for Verdasco at the US Open and Shenzhen Open in 2018, the Madrid man again got the better of the two-time Wimbledon champion, beating the Scot on an indoor hard court for the first time after five previous defeats.
It was a tough draw for Murray, who also struck unlucky at the French Open last month when he was paired with former champion Stan Wawrinka in the first round and also lost in straight sets.
The former world number one had entered the Cologne event, a low-level ATP 250 tournament, in the hope of building up match practice and registering the wins he needs to improve his ranking, which stands at 115 after his battle with injury in recent seasons.
Marin Cilic and Gilles Simon won through to the second round earlier in the day at the German event.
At the St Petersburg Open, Belarusian qualifier Ilya Ivashka survived an on-court meltdown to beat French player Adrian Mannarino 6-3 7-6 (8-6) in the first round.
Trailing 3-2 in the second set, Ivashka insisted on taking a toilet break and was penalised a game on his return to court, for delaying the match.
Ivashka explained to the chair umpire he had asked for a medical timeout because he "wasn't able to stand on court", only to be told such a break could not be used for a toilet trip.
The red mist descended as a seething Ivashka shouted: "That is not possible. It is not possible."
The punishment meant the 26-year-old fell 4-2 behind in the set, but he managed to turn around the situation to progress to the last-16 stage, where Denis Shapovalov or Viktor Troicki will await.
At the same tournament, Russian Andrey Rublev began his first week as a top-10 player by scoring a comfortable 6-2 6-4 win over Canadian Vasek Pospisil.
Milos Raonic, who skipped the French Open where Rublev reached the quarter-finals, fired 21 aces in a 7-6 (7-5) 6-1 win against JJ Wolf.
In Italy, home player Lorenzo Sonego followed up his run to the fourth round of the French Open with a 6-2 7-6 (7-4) opening win over 18-year-old compatriot Giulio Zeppieri at the Sardegna Open.
Medvedev's 6-2 6-3 victory over Japan's Yoshihito Nishioka saw him advance to the final four of the Mexican Open in Acapulco on Thursday, where he will face Rafael Nadal in a repeat of last month's Australian Open final classic.
The Russian advanced shortly after Novak Djokovic's shock loss to Jiri Vesely at the Dubai Tennis Championships, which ensured that he will start next week atop the ATP world rankings for the first time.
The news came shortly after Russian president Vladimir Putin launched a military assault on neighbouring Ukraine, an act that has attracted condemnation from across the sporting world.
"Watching the news from home, waking up here in Mexico, was not easy," Medvedev told reporters.
"By being a tennis player, I want to promote peace all over the world. We play in so many different countries. I've been in so many countries as a junior and as a pro.
"It's just not easy to hear all this news. I'm all for peace. In these moments, you understand that tennis sometimes is not that important.
"It was not easy to play and I'm happy that I managed to win the match, but it was a bit of a rollercoaster day for me."
Medvedev's compatriot Andrey Rublev had earlier spoken out in favour of peace, calling the situation "terrible" in an Instagram post.
"In these moments you realise that my match is not important," Rublev's post read. "It's not about my match, how it affects me. What's happening is much more terrible.
"You realise how important it is to have peace in the world and to respect each other no matter what, to be united.
"We should take care of our Earth and of each other. This is the most important thing."
Rublev teamed up with Ukrainian Denys Molchanov to win the Open 13 Provence doubles title in Marseille just days ago, having also won the singles title at the tournament in southern France.
Nishikori trailed 6-4 4-2 and was forced to break serve as Guido Pella attempted to close out the match in the second set, before sensationally rallying to a 4-6 7-6 (7-4) 6-2 win on Monday.
A two-time champion at the ATP 500 tournament on the Barcelona clay, Nishikori broke serve on three occasions in the final set en route to the second round.
"He had the match today at 6-5, serving [for the match]," said Nishikori. "He was much better in the first and second [sets] and 3-0 up in the tie-break. I don't know how I fought through. [In the] third set, I was playing much better.
"I was making so many unforced errors in the first and second [sets]. Maybe he got a little bit tired and I was playing strong in the third set. I want to take that to the next round… The way I fought today and the way I played in the third set was good."
Next up for 2014 US Open finalist Nishikori is 13th seed Cristian Garin.
Ilya Ivashka topped Tallon Griekspoor 6-3 6-1 and the qualifier's reward is a showdown with top seed and 20-time grand slam champion Rafael Nadal.
Cameron Norrie, Pablo Andujar, Jeremy Chardy, Pierre-Hugues Herbert, Jaume Munar, Federico Gaio, Egor Gerasimov and Bernabe Zapata Miralles all advanced to the last 32.
At the Serbia Open, seeds Filip Krajinovic and John Millman booked their spots in the round of 16.
With the ATP 250 tournament being staged for the first time since 2012 and headlined by world number one Novak Djokovic, Serbian fifth seed Krajinovic overcame Stefano Travaglia 7-5 5-7 6-3 in a Belgrade rollercoaster.
Millman – the Australian seventh seed – took down local wildcard Danilo Petrovic 7-5 6-4 as Marco Cecchinato and Nikola Milojevic won through.
Rublev beat Hubert Hurkacz 3-6 7-5 7-6 (7-5) on Friday to progress to the final of the Dubai Tennis Championships.
After confirming his place in a showdown with either Denis Shapovalov or Jiri Vesely, the 24-year-old world number seven took a pen and scribed "no to war" on the lens of a television camera.
It is not uncommon for players to write messages on camera lenses, but a plea for peace was an emotive move from Rublev.
On Thursday, Russia invaded neighbouring Ukraine following weeks of rising political tensions. The conflict escalated further still on Friday, with reports of fighting within the capital city of Kyiv.
Rublev's actions came after Medvedev – who will succeed Novak Djokovic as world number one next week – said he wanted to "promote peace".
Medvedev has reached the final four of the Mexican Open in Acapulco.
Rublev had previously expressed his wish for peace in a news conference at the Dubai event.
"In these moments you realise that my match is not important," Rublev said, with a video clip shared to his official Instagram account.
"It's not about my match, how it affects me. What's happening is much more terrible.
"You realise how important it is to have peace in the world and to respect each other no matter what, to be united.
"We should take care of our Earth and of each other. This is the most important thing."
Rublev beat Hubert Hurkacz 3-6 7-5 7-6 (7-5) on Friday to progress to the final of the Dubai Tennis Championships.
After confirming his place in a showdown with Jiri Vesely, the 24-year-old world number seven took a pen and scribed "no to war" on the lens of a television camera.
Vesely later wrote 'no war' on a camera lens after defeating Denis Shapovalov to book his place in the final.
It is not uncommon for players to write messages on camera lenses, but a plea for peace was an emotive move from Rublev.
On Thursday, Russia invaded neighbouring Ukraine following weeks of rising political tensions. The conflict escalated further still on Friday, with reports of fighting within the capital city of Kyiv.
Rublev's actions came after Medvedev – who will succeed Novak Djokovic as world number one next week – said he wanted to "promote peace".
Medvedev has reached the final four of the Mexican Open in Acapulco.
Rublev had previously expressed his wish for peace in a news conference at the Dubai event.
"In these moments you realise that my match is not important," Rublev said, with a video clip shared to his official Instagram account.
"It's not about my match, how it affects me. What's happening is much more terrible.
"You realise how important it is to have peace in the world and to respect each other no matter what, to be united.
"We should take care of our Earth and of each other. This is the most important thing."
Norrie eventually overcame the American fifth-seed after a final set tie-break, winning 6-2 1-6 7-6 (7-4).
The Brit's tenacity was key, saving seven of 10 break points, and he will now face another American, Tommy Paul, in the final four in Florida after he beat qualifier Stefan Kozlov 6-3 6-1.
The other semi-final will be contested between Reilly Opelka and John Millman after they bested Adrian Mannarino and Grigor Dimitrov respectively.
Opelka was taken to a third set by his French opponent before winning 7-6 (7-2) 3-6 6-1, hitting 19 aces on his way to victory.
Millan proved too good for third seed Dimitrov winning 6-4 6-4 in an hour and 34 minutes where the Australian's return was a highlight.
At the Rio Open, rain washed out many of the scheduled matches on Friday, with Diego Schwartzman against Pablo Andujar and Miomir Kecmanovic against Francisco Cerundolo both cancelled.
Matteo Berrettini and Thiago Monteiro were finally able to finish their round of 16 match at 11.35pm local time, with the Italian securing victory 6-4 6-7 (6-8) 6-3.
He will play seventh seed Carlos Alcaraz who overcame Federico Delbonis 6-4 7-6 (7-1) after their match was pushed back, starting not long prior to midnight local time.
Defending Rio Open champion Alcaraz was hampered by an injury to his right leg as he was pegged back after taking the opener, with Norrie eventually claiming a 5-7 6-4 7-5 win.
Alcaraz performed admirably despite seeing his movement limited in a nail-biting decider, but Norrie's power ultimately proved too much as the 27-year-old took his fifth ATP career title.
Top seed Alcaraz – playing in his 10th tour-level final at the age of 19 – started well and had forced seven break points by the time he took a thrilling first set, allowing Norrie just one.
With Alcaraz stopping to have his right thigh wrapped after appearing to be in discomfort, Norrie roared back and took the second set following three straight breaks of serve.
That teed up a dramatic finish, with Alcaraz playing a series of delightful drop shots to take the first break of the decider despite playing at walking pace for long periods.
Alcaraz stopped to tear the wrapping off his leg as the pair traded breaks in front of a lively crowd in Brazil, but it proved a bridge too far for the Spaniard as Norrie pinned him back, hitting several excellent returns to claim his first final success against a top-10 ranked opponent.
"It's so special to win this one, especially after losing a couple of finals already this year," Norrie told Amazon Prime Video. "I had to do it the tough way, you know?
"I was looking done there and I just managed to flip a switch and turn it around. It's a good day, especially on a surface I'm not too comfortable with. I had to battle a lot of demons in the last couple of weeks."
