Nadal, beaten by Roger Federer in a classic Australian Open final in January, was seeking his 70th career victory, and his third in Acapulco, though his first since the event moved from clay to hardcourt in 2014.
But after storming to the final without dropping a set, Nadal had no answer to the tall 29-year-old from California, who thumped down 19 aces and ripped a series of thundering groundstroke winners.
Querrey tore through the opening set without facing a break point in 29 minutes, seizing Nadal's serve to love in the eighth game with a crosscourt backhand winner.
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Nadal fought back in the second set, roared on a supportive crowd, but failed to convert any of his six break point opportunities.
Querrey pounced in the tiebreak to dispatch the 14-times major champion.
(Reporting by Andrew Both in Cary, North Carolina; Editing by John O'Brien)
