It is the latest in a string of hard-fought wins for Murray, who has played the maximum number of sets in each of his past 10 victories dating back to the Gijon Open in October, including a pair of five-setters at the Australian Open.
Etcheverry started strong, fresh off his first ever ATP final at the Chile Open, but committed more unforced errors (21) than winners (17) in the second and third sets combined.
Fellow Great Britain representative Jack Draper was far more comfortable in his 6-1 6-1 demolition of Switzerland's Leandro Riedi, booking an all-English clash against Daniel Evans in the second round.
Former world number three Stan Wawrinka prevailed 6-4 1-6 6-1 against Aleksandar Vukic, but Vukic's Australian compatriot Thanasi Kokkanakis flew the flag with a 6-4 6-1 triumph over hometown talent Brandon Holt.
In a better result for the Americans, Mackenzie McDonald breezed past Filip Krajinovic 6-3 6-0 in just 63 minutes, and rising 20-year-old Ben Shelton had no problems in his 6-4 6-1 win over Fabio Fognini in 72 minutes.
Argentina's Guido Pella ground out 3-6 7-5 6-2 comeback in his South American clash against Brazil's Thiago Monteiro, and Germany's Jan-Lennard Struff did the same in his European showdown against France's Quentin Halys, taking it 1-6 6-3 6-3.
There were ominous signs early on as number one seed Nadal had his serve broken in the opening game of the match, and McDonald secured a second break en route to wrapping up the first set.
It was more of the same in the second as McDonald took advantage of some uncharacteristically sloppy play from the 36-year-old, before Nadal seemed to hurt himself.
At 4-3 down in the second set, Nadal pulled up with an apparent upper leg issue after chasing a forehand, and his movement was clearly hampered from that point on.
In typical defiant fashion, Nadal's level rose in the third, hitting 24 winners, but as he improved, so did McDonald, who did not allow Nadal a single break point opportunity.
The 22-time grand slam champion saved break point at 4-4 to hold serve as he tried to get back into the contest, but was unable to repeat the trick in his next service game as McDonald secured the break before serving out to clinch a famous win.
It is the latest in a troubling run of form for Nadal, who received multiple injury timeouts on his way to a seventh loss from his last 10 matches dating back to the US Open.
McDonald will play the winner of Yoshihito Nishioka and Dalibor Svrcina in the third round.
Data Slam: Nadal joins dubious company as top-seed casualty
Nadal is the first top seed to be eliminated from the Australian Open in the second round since Gustavo Kuerten in 2001.
The Brazilian was also a clay specialist, winning all three of his grand slams at the French Open.
ACES/DOUBLE FAULTS
Nadal – 6/2
McDonald – 14/2
WINNERS/UNFORCED ERRORS
Nadal – 42/31
McDonald – 42/22
BREAK POINTS WON
Nadal – 2/4
McDonald – 5/8
World number two Nadal eased past Italian 16th seed Fabio Fognini behind closed doors at Melbourne Park in sunny and warm conditions on Monday.
Daniil Medvedev and Andrey Rublev ensured Russia made history en route to the quarters in Melbourne.
FAMILIAR TERRITORY FOR NADAL
Nadal reached the Australian Open quarter-finals for the 13th time in his career after outclassing Fognini 6-3 6-4 6-2 on Rod Laver Arena.
Stuck on 20 slam championships alongside Roger Federer, who is absent in Melbourne, Nadal is also looking to become the first man in the Open Era to win each of the four majors twice.
The 2009 Australian Open champion was too good for Fognini as Nadal continued his fine run of not dropping a set en route to the last eight in 2021.
Only at the French Open, where he is a 13-time champion, has Nadal reached the quarter-finals more often (14) than at the Australian Open. Federer (15) and John Newcombe (14) are the only men to have reached more Australian Open quarter-finals.
Nadal, who hit 24 winners against Fognini, will face fifth seed Stefanos Tsitsipas for a place in the semi-final after ninth seed Matteo Berrettini withdrew with an abdominal strain before Monday's showdown.
HISTORY FOR RUSSIA
For the first time in the Open Era, three Russian men have advanced to the quarter-finals of a slam.
Medvedev – the fourth seed – and Rublev joined countryman Aslan Karatsev in the last eight following their respective triumphs on Monday.
Runner-up at the 2019 US Open, Medvedev made light work of American Mackenzie McDonald 6-4 6-2 6-3, extending his winning streak to 18 matches as he reached his maiden Australian Open quarter-final.
"It's an exciting moment to be in the quarters in Australia for the first time. That's a great achievement for me," Medvedev said.
"I want more all the time, but step by step. So this is amazing … I finished at 1.30 [hours], which is important in the later stages of the grand slams, to make fast matches."
It will be an all-Russian affair in the quarters after seventh seed Rublev benefited from a walkover.
Rublev was leading 6-2 7-6 (7-3) when Norway's Casper Ruud retired on Margaret Court Arena.
"At least one of us will be in the semi-finals. So it's good news but yeah, it's going to be a tough match," said Rublev, who featured in last year's French Open quarter-finals.
"Last time he beat me in the quarters in the US Open. So now we're in the quarters in the Australian Open, so we'll see what's going to happen."
Former Wimbledon runner-up Berrettini beat American Mackenzie McDonald 3-6 7-6 (7-2) 6-3 at the hard court event, while Musetti came through 6-3 6-4 against Serbian Miomir Kecmanovic.
Providing Berrettini is healthy to participate in the final, the tournament looks set to deliver a crowd-pleasing trophy match, but it was touch and go whether the Rome native would get through the McDonald match.
"I don't even know how I did it," Berrettini said. "I wasn't feeling very good. I asked for the physio because my foot was hurting. It happened so many times in my career that I had to fight through so many things, not just thinking about the tennis ball."
He added, quoted by the ATP: "I didn't want to retire. My team told me, 'I think you should stop'. But I tried and I found a way."
Berrettini and Musetti have never gone head-to-head before. Berrettini has won two titles this year, both on grass, in Stuttgart and at London's Queen's Club, while 20-year-old Musetti scooped his maiden ATP title on clay in Hamburg.
At the European Open in Antwerp, Sunday's final will see American Sebastian Korda tackle Canadian Felix Auger-Aliassime, in a battle of two in-form players.
Korda was runner-up last week in Gijon, while Auger-Aliassime took the title in Florence, adding to his Rotterdam triumph from February.
Korda wrestled his way past a recently resurgent Dominic Thiem, scraping a 6-7 (4-7) 6-3 7-6 (7-4) victory, before Auger-Aliassime was given a mighty battle by veteran Frenchman Richard Gasquet, winning through in two tight sets, 7-6 (7-2) 7-6 (7-3) his margin.
Like Berrettini and Auger-Aliassime, Greece's Stefanos Tsitsipas has a third title of the year in his sights this weekend.
Tsitsipas swept through to the final of the Stockholm Open with a 6-2 6-2 win over Finland's Emil Ruusuvuori, setting up a clash with 19-year-old Danish player Holger Rune.
For Rune, there was no such straightforward path into the final as Alex de Minaur pushed him all the way, with the Australian eventually edged out 4-6 7-6 (7-1) 7-5 after two hours and 50 minutes.
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.
Fifth seed Auger-Aliassime was taken out 6-2 7-5 in one of the biggest wins of Francisco Cerundolo's career, with the Argentine avenging recent losses to the Canadian at both the Australian Open and the Indian Wells Open.
Adrian Mannarino's 7-6 (7-5) 7-6 (7-0) victory over eighth seed Hurkacz was arguably an even bigger upset, as it snapped his streak of nine consecutive losses against top-10 opponents at Masters 1000 events.
The 34-year-old Frenchman absorbed 20 aces from Hurkacz and still came out on top, limiting his own unforced errors to 13 for the match.
A third upset of the day saw unseeded Italian Lorenzo Sonego play a near faultless match to eliminate 12th seed Tiafoe, finishing the contest with 22 winners and only two unforced errors, while not facing a single break point in the brief 68-minute battle.
There was no drama for Daniil Medvedev as the fourth seed received a walkover against Alex Molcan, and he will face France's Quentin Halys in the fourth round after his 7-6 (7-2) 6-3 triumph over Mackenzie McDonald.
Two seed Stefanos Tsitsipas almost joined the long list of seeded victims, but he prevailed 6-3 4-6 6-4 against Christian Garin in the day's only three-setter.
The Greek star will meet Russian 14th seed Karen Khachanov in the fourth round after his comfortable 6-2 6-4 result over Jiri Lehecka, while unseeded American Christopher Eubanks finished the day's play with a 6-3 7-6 (9-7) defeat of Gregoire Barrere.
Francisco's younger brother Juan Martin had been eliminated by Hanfmann in the qualifying stage, but the fifth seed got one back on the German after leading the break point opportunities 17 to six.
Fifth-seed Cerundolo was the highest seed in action Tuesday, while sixth seed Sebastian Baez fell 3-6 7-6 (7-5) 6-3 to Serbia's Dusan Lajovic.
In the only all-Argentine clash it was Facundo Diaz Acosta prevailing 7-6 (7-5) 7-5 against Federico Coria – who sits over 100 places higher in the rankings – while Roberto Carballes Baena collected a seeded scalp with a 7-5 6-4 win over Spanish compatriot Albert Ramos-Vinolas.
Meanwhile, Australian Open quarter-finalist Ben Shelton was eliminated from his own hometown tournament as the Florida resident was bounced out of the Delray Beach Open 6-4 6-4 by Marcos Giron.
Shelton beat J.J. Wolf to reach that grand slam quarter-final, but Wolf will be moving on after he emerged with a 7-5 6-3 win against Ilya Ivashka.
Wolf will play France's Adrian Mannarino following his 4-6 6-3 6-4 triumph over Germany's Daniel Altmaier, and Mackenzie McDonald will get a shot at redemption against fifth seed Yoshihito Nishioka after a comfortable 6-2 6-2 success against Taro Daniel.
McDonald and Nishioka have played twice this year – once at the Adelaide Invitational and once at the Australian Open – and Nishioka has won all five sets.
It was also a day 33-year-old Matija Pecotic will never forget, with the world number 784 winning his first ever ATP Tour match by defeating Jack Sock 4-6 6-2 6-2.
Kyrgios suffered a disappointing semi-final defeat to Andy Murray in Stuttgart last week, but looked greatly improved against Tsitsipas as he recovered from a set down to win 5-7 6-2 6-4.
It was the second serve of both men where Kyrgios shone, winning 76 per cent (28 of 37) of points on his second serve, and 58 per cent (23 of 40) on his opponent's.
"Stef is one of the best players in the world at the moment and he's going to have some amazing results and I'm sure many, many grand slams," Kyrgios said following his win.
"I don't know if I can say the same for me, but I'm happy to still be able to produce this level with the tournaments I play. It is a testament to how hard I do work when I'm not playing."
He will face Pablo Carreno Busta in the quarter-finals after the Spanish sixth seed beat Sebastian Korda 6-4 0-6 6-3.
Elsewhere, Hubert Hurkacz will face Felix Auger-Aliassime in the last eight after defeating Ugo Humbert 7-6 (7-5) 6-3, while the Canadian also won in straight sets against Mackenzie McDonald 7-6 (9-7) 6-1.
The one remaining first round match saw number one seed Daniil Medvedev beat David Goffin 6-3 6-2 to set up a second round clash with Ilya Ivashka.
At the Queen's Club Championships, sixth seed Denis Shapovalov was eliminated by Tommy Paul 6-4 2-6 6-4, with the American now scheduled to face Stanislas Wawrinka in the second round.
It means that six of the eight seeds in west London were knocked out in the first round, with Matteo Berrettini and Marin Cilic the only remaining seeds. The latter sealed his place in the quarter-finals on Wednesday with a 7-6 (8-6) 7-5 win over Alexander Bublik.
Cilic will play Finland's Emil Ruusuvuori in the last eight after he beat home favourite Jack Draper 6-2 7-6 (7-2).
The best contest of the day came between Alejandro Davidovich Fokina and Alex de Minaur, with the former coming from behind to win 4-6 6-4 7-5 to set up a quarter-final with Botic van de Zandschulp, who beat Grigor Dimitrov 7-6 (7-5) 6-3.
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.
McDonald triumphed over unseeded Japanese Nishikori 6-4 3-6 7-5 in two hours and 45 minutes in Washington DC.
The 26-year-old American's win qualifies him for his maiden ATP Tour final, sending down 4-1 aces while getting a slight edge with his return.
Nishikori, who triumphed in DC in 2015, fought back when trailing a set and a break in the second with four straight games to send it to a third.
The 31-year-old Japanese appeared to have the momentum but McDonald responded to outlast him.
McDonald will face 19-year-old Sinner who overcame another emerging talent, American 20-year-old Jenson Brooksby, 7-6 (7-2) 6-1.
Sinner becomes the first Italian to reach the final in DC and also progresses to his first ATP 500 decider.
The Italian continued his fine run in DC, having not yet dropped a set all tournament, marking a return to form after being on a four-match losing run.
Sinner saved three set points at 5-6 in the first to fight back to take the lead in a tiebreaker before a dominant second.
The Canadian former world number 25 was docked a point for verbal abuse, subsequently conceding the first set, before a meltdown during the change of ends.
Pospisil used a profanity in reference to ATP chairman Andrea Gaudenzi when speaking to chair umpire Arnaud Gabas.
“[Gaudenzi was] screaming at me in a player meeting for trying to unite the players — for an hour and a half," Pospisil said to Gabas. "If you want to default me, I’ll gladly sue this whole organisation.”
He did fight back to win the second set but ultimately lost to McDonald 6-3 4-6 6-3.
Pospisil, who is nowadays ranked 67th, was joined among the first-round exits by last week's Mexican Open semi-finalist Dominik Koepfer, who went down 6-1 6-4 to wildcard Hugo Gaston as he claimed his first career Masters 1000 win.
Sam Querrey, ranked 63rd, also bowed out 6-3 6-4 to Lu Yen-hsun, who will meet world number two Daniil Medvedev in the second round.
YOUNGSTER BEATS VETERAN
Australian youngster Alexei Popyrin secured his maiden win at the Miami Open, knocking out the oldest player in the draw Feliciano Lopez 6-4 7-6 (7-4).
Popyrin, 21, claimed his first ATP Tour title last month in Singapore and backed that up with a strong display against the 39-year-old former top 20 Spaniard.
Recent Open 13 Marseille runner-up Pierre-Hugues Herbert got past Portugal's Pedro Sousa 6-1 6-3, while South Africa's Lloyd Harris defeated Emilio Nava 6-4 7-6 (9-7).
Frances Tiafoe won in the final match of Wednesday, coming from behind to beat Stefano Travaglia 5-7 6-4 6-2.
COMEBACK CAM
Brit Cameron Norrie produced a heroic final-set fightback to claim his spot in the second round, where he will face Grigor Dimitrov.
Norrie trailed 5-1 in the third set against Yoshihito Nishioka, before winning 6-1 3-6 7-5, winning the last six games to clinch victory.
The 56th-ranked Brit sent down eight aces in the victory, although he got the edge on return and converted seven of his 10 break points.
SECOND ROUND
Top seed Medvedev will face Lu on Thursday, while third seed Alexander Zverev will take on Finland's Emil Ruusuvuori.
Norrie will meet Dimitrov, while 11th seed Felix Auger-Aliassime faces Herbert and eighth seed David Goffin will take on James Duckworth.
Harris has a match-up against seventh seed Roberto Bautista Agut.
The sixth seed triumphed in two hours and 52 minutes, winning 7-5 4-6 7-5 over the unseeded American, who was competing in his first ATP Tour final.
The Washington, D.C. victory was 19-year-old Sinner's first ATP 500 title and his third on tour, having triumphed in Sofia late last year and Melbourne earlier this year.
Home favourite McDonald put plenty of pressure on Sinner, forcing the Italian to save seven break points for the match.
McDonald also staved off 16 break points in an enthralling contest where the Italian sent down nine aces to the American's five.
Sinner lost his serve twice in the opening set and needed 11 set points but still won 7-5, before the American hit back, dropping further behind the baseline to good effect in the second, levelling it with a 6-4 win.
The Italian claimed an early break in the last to open up a 3-0 lead, before failing to convert two championship points at 5-2.
McDonald brought it back to 5-5, with numerous dramatic rallies throughout, before the 2019 Next Gen ATP Finals champion broke in the 12th game to triumph in the third set.
Giron, the third seed, was a force a from the baseline, collecting 18 winners in the first set, while Etcheverry could only muster six. While he was not as dominant in the second frame, Etcheverry helped him out with 14 unforced errors and five winners.
Giron will meet James Duckworth next after the Australian defeated America's Mitchell Krueger 6-3 7-6 (7-4).
Duckworth has now won six of his past eight matches, and he showed off his impressive serve against Krueger, winning the ace count 11-to-one.
Meanwhile, Mackenzie McDonald has earned a shot against his American compatriot and second seed Jenson Brooksby after hammering Switzerland's Henri Laaksonen 6-0 6-2.
McDonald was strong in all areas, but particularly in limiting his errors, finishing the match with no double faults and six unforced errors with 19 winners.
Rising Chilean talent Alejandro Tabilo used his powerful serve to overwhelm the similarly hard-serving Steve Johnson, winning 7-5 6-2.
Tabilo served 11 aces with no double faults, and won 80 per cent (41-of-51) of his total points on serve, while Johnson had three double faults with his seven aces and could only manage a 60 per cent (34-of-57) success rate on serve.
In an all-Australian matchup, Christopher O'Connell advanced past Jason Kubler after the latter was forced to retire due to injury with the match tied at 4-6 6-3 heading into the last set.
Wu landed a 7-6 (7-1) 6-4 win against the Canadian Davis Cup winner and former top-10 player in their second-round contest.
World number 97 Wu, who this week became China's second player to reach the ATP top 100, has surged from 1,869th on the ranking list last April and believes he can crack the top 30 by the end of the year.
Speaking after getting the better of Shapovalov, who stands at 27th in the rankings, Wu said: "I've been playing great tennis the past few months. Hopefully I can keep playing good."
Frances Tiafoe cruised into the quarter-finals with a 6-1 6-3 win over fellow American Mackenzie McDonald.
Second seed Tiafoe was playing for the first time since his third-round elimination to Karen Khachanov at the Australian Open last month.
He faced just one break point in the entire match and needed just 59 minutes to deal with the world number 59.
J.J. Wolf, seeded sixth, will face Tiafoe in the last eight after he saw off Romania's Radu Albot in a 6-3 7-6 (7-5) win.
At the Cordoba Open, fifth seed Pedro Cachin was the biggest casualty on Wednesday as he was beaten 6-3 6-4 by Bolivian qualifier Hugo Dellien.
Seventh seed Pedro Martinez was also ousted in the first round, while Bernabe Zapata Miralles was sent packing by Tomas Barrios Vera in the last 16, losing 5-7 6-4 6-3.
Fourth seed Sebastian Baez had no such issues with Italy's Luciano Darderi, however, reaching the quarter-finals as a 6-3 6-4 winner.
Medvedev – the US Open champion – has lost only three of his last 41 sets, and has never dropped one to McDonald in five career meetings with the American as he maintained his red-hot form.
Russian star Medvedev is now 37-5 on hardcourts this year and appears well-positioned to make it past the third round of the ATP Masters 1000 tournament for the first time as he awaits Filip Krajinovic.
"I'm actually really pleased, because usually I haven’t played well in Indian Wells and I haven’t been playing that well in practices before [the tournament]," Medvedev said in his on-court interview. "[I am] really happy with my performance. That’s the most important [thing] no matter how I played before the tournament."
RUBLEV ROLLS PAST TABERNER
Medvedev's countryman Andrey Rublev closed out the night session with a 6-3 6-4 defeat of Carlos Taberner, who was facing a top-10 opponent for the first time.
Fourth seed and world number five Rublev won 66 per cent of points on his first serve and hit 30 winners to Taberner's 12.
Rublev improved to 47-16 this season, 31-9 on hard courts, and will face Tommy Paul in the third round.
SHAPOVALOV WINS IN NEAR-WALKOVER
Most of the seeded players in action had an easy time of it, none more so than Canadian ninth seed Denis Shapovalov.
Shapovalov's opponent and countryman Vasek Pospisil retired with an apparent back injury after dropping the first three games of the match.
Sixth seed Casper Ruud blew past Roberto Carballes Baena 6-1 6-2, while eighth seed Hubert Hurkacz downed Alexei Popyrin 6-1 7-5.
Diego Schwartzman had to work harder to advance, the 11th seed outlasting qualifier Maxime Cressy 6-2 3-6 7-5.
Top-ranked American Reilly Opelka, the 16th seed, beat Taro Daniel 7-5 6-3 for his first main-draw victory at Indian Wells in four attempts.
Daniel Evans also went the distance to defeat Kei Nishikori 4-6 6-3 6-4, while former world number three Grigor Dimitrov, 2021 Australian Open semi-finalist Aslan Karatsev and Frances Tiafoe were among the other players to advance.
The Italian managed a 2-6 6-2 6-1 6-2 victory over the world number 140, having looked well off the pace in the opening set.
McDonald's fellow American Alex Michelsen awaits in the second round for Sinner, who triumphed in his first major match since an independent tribunal cleared any wrongdoing from positive tests for banned substances.
The world number one may have been impacted by those ongoing off the court and was slow to get going, dropping his serve three times en route to a first-set concession.
Sinner held off seven break-point opportunities from the home favourite in that opener, and improved from then on, losing on his serve just once in the second set.
The 23-year-old never looked back from that second-set clincher, easing to victory in just under two-and-a-half hours.
Data Debrief: Super Sinner flying
Sinner, who won his maiden major trophy at the Australian Open in January, is now 49-5 for the season after an impressive 2024.
That run includes lifting a third ATP Masters 1000 crown in Cincinnati last week, where he overcame his next opponent Michelsen in the pair's only ATP Tour meeting to date.
