Top seeds David Ferrer and Kei Nishikori bowed out of the Abierto Mexicano Telcel in the second round.
A four-time champion in Acapulco, including last year, Ferrer was a surprise 6-4 6-4 loser to Ukraine's Alexandr Dolgopolov on Wednesday.
Dolgopolov converted three of 10 break points on the hard-courts at the ATP 500 event, booking his place in the quarter-finals.
Awaiting him is Dutchman Robin Haase, who battled past Aljaz Bedene 6-4 6-7 (3-7) 6-4.
The tournament is wide open after Nishikori, last year's runner-up, joined Ferrer in making a surprisingly early exit.
The Japanese second seed was well beaten by American Sam Querrey 6-4 6-3.
Querrey will face countryman and 18-year-old rising star Taylor Fritz, who reached the Memphis final before losing to Nishikori.
Fritz was too good for Victor Estrella Burgos 6-1 6-3 in their second-round clash.
Setting up a blockbuster last-eight meeting were the in-form Dominic Thiem and Bulgarian seventh seed Grigor Dimitrov.
Thiem edged past Dmitry Tursunov 6-7 (5-7) 6-3 6-4, while Dimitrov brushed past Donald Young 6-3 6-4.
Australian fifth seed Bernard Tomic advanced with a 6-4 6-4 victory over Adrian Mannarino and will face Illya Marchenko, who needed almost three hours to overcome Ryan Harrison 7-6 (7-3) 4-6 7-6 (7-5).