Nadal squandered three match points, and Kyrgios, now world No. 72, scored a huge upset.
ACAPULCO, Mexico — Rafael Nadal tumbled out of the Mexican Open on Wednesday night, squandering three match points in a 3-6, 7-6 (2), 7-6 (6) loss to Australia's Nick Kyrgios.
Playing his first event since losing to Novak Djokovic in late January in the Australian Open final, the top-seeded Nadal dropped the first two match points on Kyrgios' serve and the last one on his own first serve.
Nadal won in Acapulco in 2005 and 2013. On Tuesday night, the second-ranked Spanish star opened play with a 6-3, 6-3 victory over Mischa Zverev.
Kyrgios set up a quarterfinal match against Stan Wawrinka, a 7-6 (5), 6-4 winner over seventh-seeded Steve Johnson in the hardcourt event at The Princess Mundo Imperial.
The top seed also fell in the women's event, with Brazilian qualifier Beatriz Haddad Maia beating Sloane Stephens 6-3, 6-3 for her first victory in seven career matches against players ranked in the top 10. The fourth-ranked Stephens, the 2017 U.S. Open, was making her first appearance in the event since winning the 2016 title.
''It was just a tough match, obviously she played well,'' Stephens said. ''A tough day. But I'm not too sad about it. I'm just going to go back and work some more, practice some more and get ready for Indian Wells.''
Haddad Maia will face Wang Yafan in the quarterfinals. Wang led Monica Puig 4-1 when Puig retired because of an injury.
In men's play, second-seeded Alexander Zverev beat David Ferrer 7-6 (0), 6-1 in the late match. He will play fifth-seeded Alex de Minaur, a winner over Feliciano Lopez in a walkover.
Third-seeded John Isner beat fellow American Sam Querrey 6-4, 6-4 to set up a quarterfinal match against eighth-seeded John Millman. Millman beat Peter Gojowczyk 6-0, 6-2.
Cameron Norrie beat fourth-seeded Diego Schwartzman 7-6 (5), 4-6, 6-3. Norrie will face Mackenzie McDonald, a 6-7 (7), 7-5, 6-3 winner over sixth-seeded Frances Tiafoe.
Defending champion Juan Martin del Potro is sidelined by a knee injury.
In women's play, two-time Australian Open champion Victoria Azarenka routed Tatjana Maria 6-2, 6-1 to set up a quarterfinal against fifth-seeded Sofia Kenin. Kenin led 6-4, 4-1 when Katie Boulter retired.
Third-seeded Donna Vekic advanced with a 6-4, 7-5 victory over Christina McHale; Bianca Andreescu topped fourth-seeded Mihaela Buzarnescu 6-2, 7-5; seventh-seeded Saisai Zheng edged Timea Babos 4-6, 6-4, 6-3; and eighth-seeded Johanna Konta beat Varvara Flink 6-4, 6-1.
In the quarterfinals, Vekic will play Konta, and Zheng will meet Andreescu.
Lesia Tsurenko, the women's winner the last two years, is skipping the event.