The highly rated Spanish teenager eventually downed the German wildcard 3-6 6-1 7-6 (7-3).
Kuhn, ranked 259 in the world, was aggressive early on against Alcaraz, and was rewarded with the first set.
But the 19-year-old – playing as top seed in an ATP Tour event for the first time – rallied to ease through the second set, before being made to work much harder to clinch the win on a tie-break.
Alcaraz will now play Filip Krajinovic in the second round after the Serbian also won in a third-set tie-break against Sebastian Baez 6-1 4-6 7-6 (8-6).
Three seeded players crashed out on Tuesday in straight sets, with third favourite Diego Schwartzman losing against Emil Ruusuvuori 7-5 6-4, sixth seed Nikoloz Basilashvili beaten by Aslan Karatsev 6-4 6-0, and eighth seed Holger Rune going down 7-6 (10-8) 7-5 to Tallon Griekspoor.
Fourth seed Pablo Carreno Busta eased through against Luca Nardi 6-2 6-1, while there were also wins for Fabio Fognini, who sealed his 400th career victory, as well as Daniel Elahi Galan, Borna Coric and Francisco Cerundolo.
At the Swiss Open in Gstaad, sixth seed Cristian Garin lost 6-3 6-4 to Yannick Hanfmann and seventh favourite Hugo Gaston fell to Dominic Thiem despite winning the first set, losing 1-6 6-1 7-6 (9-7).
Elsewhere, Frenchman Richard Gasquet beat Roberto Carballes Baena 7-5 6-4, while his compatriot Benoit Paire retired hurt when a set and a break down against Elias Ymer.
A tight game between Swiss pair Dominic Stricker and Marc-Andrea Huesler saw the former prevail 6-7 (2-7) 7-6 (7-2) 6-4, and an all-Spanish affair was similarly close as Jaume Munar defeated Bernabe Zapata Miralles 6-3 3-6 7-5.
There were also wins for qualifiers Juan Pablo Varillas and Nicolas Jarry against Lorenzo Sonego and Thiago Monteiro respectively.
Baez took a set off Stefanos Tsitsipas – his first ever top-10 opponent – before losing at the Australian Open, but he has kicked on again in Argentina.
The 21-year-old faced a huge uphill battle when he fell a set behind to third seed Garin, who won in Cordoba in 2020.
However, Baez roared back in quite remarkable fashion to prevail 4-6 6-1 6-1 in perhaps the best result of his career – and one of his opponent's worst.
"It was a pretty bad match, one of the worst of my career in terms of feeling," Garin said. "He deserves it as well, but I feel like I wasn't up to it.
"I had a regular first set and then I couldn't find myself. The little adaptation I had was clear, I was slow. It was one of my worst matches in many years."
Baez faces Alejandro Tabilo next after his last-16 defeat of Carlos Taberner, but a tricky field remains as the two seeds in action besides Garin on Thursday both won.
The reward for Lorenzo Sonego and Albert Ramos-Vinolas is a match against one another on Friday.
2017 runner-up Joao Sousa cruised past Vit Kopriva 6-1 7-5 and Jurij Rodionov set up a Round of 16 meeting with third seed Roberto Bautista Agut with a straight-sets victory over Hernan Casanova.
Dominic Thiem, who won the 2019 edition of the competition, will face Alexander Shevchenko tomorrow while Richard Gasquet will take on Sebastian Ofner.
2016 Croatia Open winner Fabio Fognini will not be regaining his title in Umag this year, after the seventh seed was knocked out by Colombian Daniel Galan in a 3-6 7-5 3-6 defeat.
Galan will play Giulio Zeppieri in the next round, who came from one set down to overcome world number 90 Pedro Cachin 3-6 6-1 6-4.
Fifth seed Alex Molcan plays his first game tomorrow against Duje Adjukovic, and sixth seed Daniel Altmaier will take on French 23-year-old Corentin Moutet.
Fritz, the third seed, faced sixth seed and world number 15 Frances Tiafoe, and did not allow a single break of serve en route to the 96-minute victory.
He will now face compatriot Tommy Paul in an all-American semi-final after the world number 23 prevailed 6-2 6-2 against Mackenzie McDonald.
The win was Paul's 10th from his past 12 matches, with one of those two losses coming against Novak Djokovic.
Australia's Alex De Minaur is through to the other semi-final after making light work of Japan's Taro Daniel 6-2 6-2 in a surprisingly one-sided contest, considering Daniel was coming off a victory over world number four Casper Ruud.
De Minaur will face Holger Rune after the 19-year-old capitalised on Matteo Berrettini not being at 100 per cent, jumping out to a perfect 6-0 1-0 start before the Italian retired hurt.
Meanwhile, Chile Open second seed Francisco Cerundolo missed out on a potential chance to face his younger brother after going down 6-3 3-6 6-3 against Tomas Martin Etcheverry.
He was one win away from doing his part to set up a quarter-final showdown with Juan Manuel Cerundolo, but the 21-year-old Argentine also did not hold up his end of the bargain, falling 6-2 2-6 7-6 (7-2) to Serbia's Dusan Lajovic.
Laslo Djere ensured it would be a good day for the Serbians with a 7-5 7-5 handling of Italy's Riccardo Bonadio, and he will face third seed Sebastian Baez in the quarter-final after he eliminated hometown hero Cristian Garin 6-4 6-3.
Fresh off his maiden ATP 1000 title at Indian Wells and fourth-round run in Miami, the American world number 13 needed just 62 minutes to win in straight sets, in his first clay court match for the season.
Fritz's serve was not particularly secure, though, with the unseeded Tabilo converting on only one of six break point attempts. Fritz was more efficient and assertive when opportunities presented on the other hand, taking two of three break point chances on Tabilo's serve while winning 12 out of 19 points returning on his second serve.
Despite the Chilean world number 100 fighting back to 4-4 from 3-0 down in the second set, Fritz steadied to close out the match.
"I felt like tonight was going to be a really tough match, given he's done really well on clay," Fritz said post-match. "It was my first match [on clay]. I'm pretty happy with how I played. I can't complain, I got out of that pretty solid."
Fritz will now face another Chilean, fifth seed and defending champion Cristian Garin, who came back from a set down to defeat Jordan Thompson 3-6 6-3 6-3.
Entering the Houston event on a five-match losing streak, Garin has come from behind in back-to-back matches to win.
Sixth seed Frances Tiafoe also went the distance on Thursday, earning a 5-7 7-5 7-6 (7-4) win over Uruguayan Pablo Cuevas.
With neither garnering break point chances in the third set, Tiafoe finally created breathing room by winning four straight points at 2-2 in the deciding tie-break, before closing out the match.
It sets up an all-American quarter-final with John Isner, who defeated Steve Johnson 6-7 (1-7) 7-6 (7-4) 6-3 in Thursday's final game.
Slotted into the primetime fixture, Santiago resident Garin did not let the locals down, securing a break in the first game of the match to set the tone.
The other Chilean hopeful in the field, Nicolas Jarry, kept up his terrific form to also book his place in the second round.
After making the semi-final of last week's Rio Open – where he took a set off world number two Carlos Alcaraz – Jarry beat Peru's Juan Pablo Varillas 7-6 (7-1) 6-4 for an 11th victory from his past 14 matches.
Fifth seed Albert Ramos-Vinolas was the highest ranked player in action, and he went down 7-5 4-6 7-5 against Brazil's Thiago Monteiro, while sixth seed Laslo Djere had a better outing in his 6-3 6-2 victory over Joao Sousa.
Tomas Martin Etcheverry will meet second seed Francisco Cerundolo in an all-Argentine second round matchup after advancing past Italy's Fabio Fognini 6-1 7-6 (7-1).
Meanwhile, in Acapulco at the Mexican Open it was the Berrettini brothers stealing the headlines on a day where top hopes Carlos Alcaraz and Cameron Norrie both withdrew due to injuries.
World number 24 Matteo Berrettini won the first seven games of his match against Alex Molcan before the Slovak decided to retire at 6-0 1-0, and his younger brother Jacopo Berrettini capitalised on his qualifier status with a 3-6 7-6 (7-3) 2-1 (retired) comeback against Oscar Otte.
Australian eighth seed Alex De Minaur was the top seed in action and he discarded of Mexico's own 17-year-old qualifier Rodrigo Pacheco Mendez 6-1 6-2, while rising 21-year-old American Brandon Nakashima overcame Germany's Daniel Altmaier 6-3 3-6 6-1.
Fifth seed Garin – winner of the most recent edition in 2020 – exited a second consecutive tournament at the first-round stage after he was humbled by Federico Coria.
Coria had defeated the fifth seed, Dusan Lajovic, at last week's Argentina Open, too, but was particularly impressive on Tuesday.
A stunning 6-2 6-0 win was sealed in an hour and 16 minutes.
Coria fended off two break points midway through the first set and then won the remaining nine games in succession in a dominant victory.
Garin was the only seed to lose in Brazil, however, as Lorenzo Sonego was on the right side of a 6-2 6-0 scoreline against 2019 winner Laslo Djere.
Fabio Fognini also advanced in straight sets, while Spanish pair Albert Ramos-Vinolas and Fernando Verdasco similarly eased through.
At the Delray Beach Open, 2021 runner-up Sebastian Korda defeated Thanasi Kokkinakis in his first match since winning the Australian Open doubles title with Nick Kyrgios.
Former champion Sam Querrey came up short against Denis Istomin.
The Chilean fifth seed, who was the highest-ranked player in action, is regarded as one of the ATP Tour's best on clay but hardly got a look-in as 18-year-old Rune emerged with an impressive 6-3 6-1 win.
Rune has risen to a career-high 72 in the ATP rankings and showed every sign that he will continue to climb over the season as he produced an aggressive performance that saw him take six of 17 break points.
Playing in only his fifth ATP Tour match on clay, Rune needed just an hour and 25 minutes to see off Garin – the winner of five tour-level titles on the surface – and set up a second-round clash with either Dusan Lajovic or Taro Daniel.
Sixth and seventh seeds Fabio Fognini and Miomir Kecmanovic avoided similar shocks, though their respective wins were wildly different.
Kecmanovic crushed veteran Richard Gasquet 6-0 6-3, while Fognini was forced to overturn a one-set deficit in his defeat of fellow Italian Marco Cecchinato 6-7 (5-7) 6-2 6-2.
No seeds were in action at the Barcelona Open, but Italian prospect Lorenzo Musetti enjoyed a hard-fought 7-5 7-5 defeat of Argentina's Sebastian Baez to seal his spot in the second round.
The 20-year-old is now 5-2 for the clay season and will go up against Dan Evans next. Joining Musetti in progressing is another promising youngster in Brandon Nakashima, who beat Nicolas Alvarez Varona 7-6 (8-6) 6-3 to tee up a clash with number two seed Casper Ruud.
Mackenzie McDonald, Elias Ymer, Kwon Soon-woo and Federico Coria were among the other victors, while retiring 2004 champion Tommy Robredo bowed out with a 6-1 6-1 loss to Bernabe Zapata Miralles.
The biggest names in the field learned their opponents after the 32 seeded entrant received byes into the second round of the Masters 1000 event, and Tsitsipas will be desperate to avoid a third consecutive loss after quick exits at the Rotterdam Open and Indian Wells Open in recent weeks.
Fourth seed Daniil Medvedev is waiting for Roberto Carbellas Baena after he blew away Bernabe Zapata Miralles 6-0 3-0 (retired) in an all-Spanish showdown, while fifth seed Felix Auger-Aliassime will meet Brazil's Thiago Monteiro in the second round after his 6-4 7-6 (8-6) triumph over Australia's Jason Kubler.
After O'Connell and Kubler both fell, Thanasi Kokkinakis flew the flag for Australia with a 4-6 6-3 7-6 (9-7) comeback against Belgian wildcard Zizou Bergs, and his reward will be a battle against Polish eighth seed Hubert Hurkacz.
France's Gregoire Barrere earned a big matchup against 11th seed Cameron Norrie after eliminating Roman Safiullin 6-4 3-6 6-3, and Safiullin's Russian compatriot Pavel Kotov will join him on an early flight home after going down 6-2 6-2 against recent Chile Open finalist Tomas Martin Etcheverry.
Rune was beaten by Marc-Andrea Huesler in the final of the last tournament he entered in Sofia following a quarter-final appearance in Metz.
The Danish teenager, who last week announced Patrick Mouratoglou had joined his team for the rest of this season, defeated Monteiro 7-5 6-2 on his debut in the Swedish capital.
Rune did not face a break point and won 86 per cent of points on his first serve as he booked a meeting with Cristian Garin.
Garin beat qualifier Jason Kubler 6-2 6-4, while Maxime Cressy and Aslan Karatsev advanced to the last 16 at the expense of Ilya Ivashka and Lukas Rosol respectively.
Richard Gasquet consigned Stan Wawrinka to an early exit at the European Open, coming from a set down to win 2-6 7-6 (7-4) 6-4 in a battle of two of the most experienced players on the circuit.
Fifth seed Dan Evans beat Tallon Griekspoor 6-3 6-4 in the first round in Antwerp, while his fellow Brit Jack Draper was an emphatic 6-1 6-2 winner against Jenson Brooksby of the United States.
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.
After coming from a set down to force a decider against Lloyd Harris in his opening match in Rome, Karatsev held serve when facing match point in a back-and-forth tie-break.
The Russian had already missed a chance to break for the match but did not fail at the second attempt, completing a 3-6 6-3 7-6 (9-7) win to book a date with world number one Djokovic.
Djokovic will be eager to get back on track after suffering a defeat to Carlos Alcaraz in the semi-finals of the Madrid Open.
Filip Krajinovic's reward for a 7-6 (9-7) 7-6 (7-4) victory over Frances Tiafoe is a showdown with Andrey Rublev, while Cristian Garin will take on the in-form Alcaraz following a 6-3 6-2 success over wildcard Francesco Passaro.
Marin Cilic was the other main-draw winner on Sunday, cruising past Matteo Arnaldi 6-1 6-4 in an hour and 20 minutes.
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.
The highest-ranked Brazilian in the field made a winning start at South America's only ATP 500 event, but he had to work for it, emerging victorious after an 88-minute third set.
A raucous crowd cheered on every point down the stretch, and after saving four break point opportunities to force a tiebreaker, he jumped ahead to a 5-1 advantage and served it out.
He will face the winner between second seed Cameron Norrie and rising Argentine talent Juan Manuel Cerundolo in the next round.
Meanwhile, the top seed in action on Monday – third seed Lorenzo Musetti – continued his recent rough stretch of form with a disappointing 6-4 6-1 defeat at the hands of Chile's Nicolas Jarry.
Musetti, already ranked 18th in the world at 20 years old, has now lost four of his past five matches, while Jarry has won eight out of 10.
Jarry will play Spain's Pedro Martinez in the second round after he spoiled a potential all-Chilean matchup, eliminating Cristian Garin 7-6 (7-0) 6-4.
The only other Brazilian in action, Joao Fonseca, had no luck against Slovakia's Alex Molcan as he went down 6-0 6-3, while Bolivia's Hugo Dellien was similarly dominant in his 6-0 6-2 trouncing of Portugal's Joao Sousa.
After taking a set off world number two Carlos Alcaraz at last week's Argentina Open, Laslo Djere advanced into the second round as Facundo Bagnis retired in the second set while trailing 6-2 3-2.
World number two Nadal, chasing a record-extending sixth title on home soil, advanced 6-3 6-3 in a time of one hour and two minutes on Thursday.
Popyrin, playing in his first last-16 match at a Masters 1000 event, broke Nadal in the sixth game of the opening set but the Spaniard otherwise looked comfortable.
Nadal converted four of his six break points to advance through to the last eight for a 15th time, where Alexander Zverev awaits.
"It was difficult," Nadal said in his on-court interview. "The court today was slippery, it was very fast, very dry conditions. The ball was flying a lot. The beginning was super tough.
"He was hitting every ball and hitting the spots. I'm happy with the victory. It was an important victory, he came here playing well. Every match is tough."
Zverev, who won the competition in 2018, beat British number one Dan Evans 6-3 7-6 (7-3) to set up a meeting with Nadal
However, second and fourth seeds Medvedev and Tsitsipas saw their participation come to an end at the hands of Cristian Garin and Casper Ruud respectively.
Medvedev, who is still yet to reach the quarters in Madrid, lost the only break of serve in the third game of the opening set but recovered by taking the second set in a tie-break.
Garin dominated the deciding set, the world number 25 breaking Medvedev twice and, after a short delay to fix a broken net, advanced 6-4 6-7 (7-2) 6-1.
Tsitsipas, who held championship point against Nadal in the Barcelona Open final, failed to break Ruud on a single occasion as he fell 7-6 (7-4) 6-4.
Alexander Bublik is next up for Ruud after beating Aslan Karatsev 6-4 6-3, while Matteo Berrettini - 7-6 (7-4) 6-4 winner against Federico Delbonis - will meet Garin.
Also vying for a place in the semi-finals are John Isner and Dominic Thiem, who are set to face off after beating sixth seed Andrey Rublev and Alex de Minaur respectively.
'King of Clay' Nadal fell to a 1-6 7-5 6-2 defeat to Shapovalov in the third round in Rome, with the Canadian surging to victory after winning 12 straight points from 2-2 in the deciding set.
The legendary Spaniard stormed through the first set thanks to a series of brilliant returns, but his opponent dominated at the net in the second to take the match the distance.
Shapovalov then flipped the narrative on its head by winning 14 of a possible 22 return points to set up a quarter-final meeting with Casper Ruud, who beat Jenson Brooksby 6-3 6-4.
Djokovic is one win away from retaining his status as world number one after taking just 75 minutes to see off three-time grand slam winner Stan Wawrinka 6-2 6-2.
After a lengthy spell out injured, Wawrinka ended a 15-month wait for an ATP Tour victory at Foro Italico before the Serbian brought his run to an end.
"It is great to see Stan back and winning. He won two tough matches. You can see he is still not physically where he wants to be. But, nevertheless, he is Stan Wawrinka and he can hurt you if you give him time," Djokovic said.
"I managed to do well from the beginning. I really moved him around the court and held my serve comfortably except for that loss of my serve in the second set."
Felix Auger-Aliassime stands between Djokovic and the number one spot after overcoming lucky loser Marcos Giron 6-3 6-2.
In the other half of the draw, Stefanos Tsitsipas and Jannik Sinner will play out an entertaining quarter-final after they beat Karen Khachano and Filip Krajinovic respectively.
Alexander Zverev, the defeated finalist in Madrid last week, beat Alex De Minaur 6-3 7-6 (7-5) and will battle Cristian Garin for a place in the final four.
Nadal, a five-time champion at the event, was a break up in the first set of his 15th quarter-final at Caja Magica but lost 6-4 6-4 in an hour and 44 minutes.
The win was the biggest of Zverev's career on clay and confirmed his rise to second in the ATP Rankings.
While Nadal said he was largely pleased with his displays in the Spanish capital, he was at a loss to explain the manner of his defeat on Friday.
"I'm leaving Madrid with an overall positive feeling, but at the same time with the ugly feeling of having played a match like this today against a great player," Nadal told a media conference.
"I think for most of the first set, I was playing better than him. And this is the negative part; while playing better than him in the first set, I still lost 6-4.
"This is very difficult to understand, especially for me. When this happens to me, it's usually in the opposite way. I find a way to win sets even though I'm not playing my best or as good as the opponent.
"I felt like I was playing better for much of the first set, but after a couple of errors – unjustifiable errors at the worst times – I found myself down a set.
"The outlook of the match changed there, both for me and for him. I knew then that a lot of suffering was waiting for me [in the second set], and for him, the knowledge that he just took a huge step forward during the match."
Zverev will face Dominic Thiem in the last four after the Austrian overcame John Isner 3-6 6-3 6-4 in an hour and 55 minutes.
Thiem, who has now made it to the past four Madrid Open semi-finals, said: "I think we all know that he is one of the best servers in history and the altitude here in Madrid makes it even tougher to return his serve.
"I was a little bit surprised by his return games. I think he actually attacked both of my serves, the first and the second, and it took me a while to get used to it."
Casper Ruud will meet Matteo Berrettini in the other semi-final.
Norwegian Ruud eased past Alexander Bublik 7-5 6-1 to make it three consecutive clay ATP Masters 1000 semis, while Berrettini beat Cristian Garin 5-7 6-3 6-0.
Opelka kept up his strong early-season form with an imposing 6-3 7-5 victory over Nick Kyrgios in the first semi-final, getting the job done in just one hour and nine minutes.
Opelka slung down 18 aces to 11 from Kyrgios and faced only one break point across the contest.
The 24-year-old Opelka won a title in Dallas in February and followed up with a run to the Delray Beach final, with a third trophy match of the season now awaiting him.
The American world number 18 said he admired the "intangibles" from Kyrgios that "you can't teach."
"He's got one of the best serves in the world and when he turns it on he can come up with some shots that not many guys outside the top 10 can," Opelka said in his on-court interview.
Opelka enjoyed the high-tempo match with Kyrgios, who typically wastes no time between points.
"I prefer to play at that speed rather than, for example, Rafa [Nadal] where it's 50-55 seconds between points," Opelka said.
"It's a totally different speed here and I thought I did a good job managing the whole tempo of the match. I put a lot of returns into play and I came up big with my second serve."
He will face 2013 Houston champion Isner, who came from a set down to defeat defending champion Cristian Garin 4-6 6-3 6-4.
The 36-year-old's serve improved as the match went on and ultimately propelled him to victory, facing four break points in the opening set, one in the second and none in the decider.
Isner also served 17 aces on his way to the final, and won 80 per cent of points on his first serve.
"It's never easy when you have to come back from one set down," he said. "My serve certainly helped me out a lot. I didn't have to hit too many balls there in the end, and I didn't want to.
"I'm so happy to be in the final again here. At my age you never really know when you can get back to a final of a tournament like this."
The giant American, who measures in at six-foot-11, was terrific in the opening set, winning 84 per cent of his successful first serves (16-19) and allowing no break point opportunities.
The second set was much more competitive, as Brouwer broke first to go up 3-1, but Opelka answered instantly and then grabbed the match-winning break when 6-5 up to avoid a tie-breaker.
Opelka will face a fresh Nick Kyrgios in the semi-final after the Australian was gifted a walkover win against Michael Mmoh due to injury.
In a clash between two top-five seeds, world number 29 Christian Garin got the better of world number 13 Taylor Fritz 6-2 6-7 (5-7) 6-3.
What made Garin successful in the first and third sets was his return game, winning more than half of his return points in those sets combined (26-51).
Fritz had chances to get back into the game, but Garin saved 11 of 14 break point opportunities, including six of seven in the deciding third set.
Garin will play American John Isner in the semi-final after Isner triumphed in a three-set battle against Frances Tiafoe 6-4 2-6 6-3.
Isner's trademark serve was inconsistent, and abandoned him in a grim second-set performance, winning just 11 of 21 service points on his way to getting broken twice to allow Tiafoe to force the match into a third frame.
In Isner's two successful sets, he won more than 80 per cent of his first serves (35-41), and allowed no break point opportunities in the third.
Ruud, the third seed, joined second seed Stefanos Tsitsipas with an early exit after a timid display, with just 17 winners to go with 17 unforced errors against Chile's Garin.
Meanwhile, Garin took his opportunity against the world number four with both hands, rattling off 39 winners with 24 unforced errors as he made the decision to take the match on and not die wondering.
Garin, who already defeated 29th seed Yoshihito Nishioka in the second round, will meet his third seeded opponent in a row in the quarter-final when he takes on Spain's 23rd seed Alejandro Davidovich Fokina.
Davidovich Fokina eliminated 13th seed Karen Khachanov 6-3 1-6 6-4, but it was still a strong day for the Russians as top hopefuls Daniil Medvedev and Andrey Rublev advanced.
Medvedev, the fifth seed, was tested in his 6-2 3-6 6-1 victory over Belarus' Ilya Ivashka, while sixth seed Rublev saw off France's Ugo Humbert 7-5 6-3 without much issue.
Waiting for Rublev in the quarter-final is Briton Cameron Norrie after his 6-7 (5-7) 7-5 6-2 battle against Taro Daniel, while Alexander Zverev beat Emil Ruusuvuori 7-5 1-6 7-5 to book a tantalising clash with Medvedev.
In a poor day for the Australians, Jason Kubler went down 6-3 6-2 against 14th seed Frances Tiafoe, and Jordan Thompson could not follow up his incredible upset against Tsitsipas, falling 6-3 7-6 (8-6) to Chile's Alejandro Tabilo.
