Mexico City - Kei Nishikori, who was coming off a title run at Memphis less than two weeks ago, bombed out of the Abierto Mexicano Telcel, losing 6-4, 6-3 to Sam Querrey on Wednesday.
Querrey advances to his third straight ATP Tour quarter-final where he will face American teenager Taylor Fritz.
It is the first time in four tournaments this season that Japan's Nishikori has not reached at least the quarter-finals.
"It's always hard when you play against good players, but it wasn't my day today," the second seeded Nishikori said.
"There were many things that I should do better, especially my serve.
"I wasn't aggressive enough to beat Sam today. Also he was hitting really big serves so there weren't many chances for my return game."
Nishikori's ouster means the tournament is without its top two seeds after David Ferrer's earlier loss to Alexandr Dolgopolov.Results on Wednesday in the ATP and WTA Mexico Open at Acapulco (x-denotes seeded player):
Alexandr Dolgopolov (UKR) bt David Ferrer (ESP x1) 6-4, 6-4
Bernard Tomic (AUS x5) bt Adrian Mannarino (FRA) 6-4, 6-4
Illya Marchenko (UKR) bt Ryan Harrison (USA) 7-6 (7/3), 4-6, 7-6 (7/5)
Grigor Dimitrov (BUL x7) bt Donald Young (USA) 6-3, 6-4
Sam Querrey (USA) bt Kei Nishikori (JPN x2) 6-4, 6-3
Robin Haase (NED) bt Aljaz Bedene (GBR) 6-4, 6-7 (3/7), 6-4
Taylor Fritz (USA) bt Vctor Estrella (DOM) 6-1, 6-3
Dominic Thiem (AUT) bt Dmitry Tursunov (RUS) 6-7 (5/7), 6-3, 6-4
Dominika Cibulkova (SVK) bt Victoria Azarenka (BLR x1) walkover
Anastasia Pavlyuchenkova (RUS x3) bt Julia Glushko (ISR) 6-2, 6-1
Naomi Osaka (JPN) bt Mariana Duque (COL) 6-3, 7-6 (7/5)
Sloane Stephens (USA x2) bt Olga Govortsova (BLR) 6-4, 6-1
Mirjana Lucic-Baroni (CRO) bt Johanna Konta (GBR x4) 4-6, 6-2, 7-5
Christina McHale (USA) bt Danka Kovinic (MNE x7) 3-6, 6-3, 6-2
Johanna Larsson (SWE x6) bt Shelby Rogers (USA) 6-1, 6-7 (2/7), 7-5
Yanina Wickmayer (BEL x8) bt Monica Puig (PUR) 3-6, 6-3, 6-3