Croatia's Ivo Karlovic won the battle of the big servers, dumping third seed John Isner from the Abierto Mexicano on Tuesday.
Isner was the highest-ranked player to lose on Tuesday with Canada's Vasek Pospisil (seeded eight) losing to in-form Ukrainian Alexandr Dolgopolov 6-2, 6-2.
Top seed David Ferrer had few troubles accounting for Mikhail Kukushkin 6-2, 6-3. Fourth seed Grigor Dimitrov overcame Marinko Matosevic 7-5, 6-1 and fifth seed Kevin Anderson trumped Stephane Robert 6-2, 7-6 (9-7).
Second seed Andy Murray survived after losing the first set to Pablo Andujar to triumph 3-6, 6-1, 6-2 in just over two hours.
Karlovic sent down 15 aces, while Isner managed eight, as the former won 7-6 (7-4), 7-6 (7-5) in Acapulco.
In both tiebreakers, Karlovic took control early and never relinquished the upper hand as he eliminated the 28-year-old American in 1:40.
Karlovic led 3-0 in the first tie-breaker and then 4-1 in the second to set up his victory.
The 34-year-old Croatian won 84 percent of points on serve. Isner could only manage 74 percent in a very tight match that involved just two breaks.
Karlovic will take on Israel's Dudi Sela next at the ATP 500 event.
Dolgopolov made the final of last week's Rio Open but lost the tournament decider to world number one Rafael Nadal.
Jeremy Chardy of France will be Dolgopolov's next opponent.
Gilles Simon, the sixth seed, defeated Tim Smyczek 6-1, 6-2 and seventh seed Ernests Gulbis crushed Yen-Hsun Lu 6-1, 6-1.
Feliciano Lopez will clash with fellow Spaniard Ferrer in the next round after knocking off Edouard Roger-Vasselin 6-4, 6-2, while David Goffin trumped Lukasz Kubot 6-2, 2-6, 6-4.
Lucky loser Donald Young stunned Jarkko Nieminen 6-3, 6-3 after Jurgen Melzer pulled out to give the American lefty a main-draw lifeline, Marcos Baghdatis defeated Miguel Angel Reyes-Varela 6-2, 6-4 and Joao Sousa won 1-6, 6-2, 6-2 over Adrian Mannarino.