The third-seeded Swiss dominated the left-handed Verdasco with his punishing groundstrokes and solid service game to claim a measure of revenge with a 7-6(4) 6-4 6-4 victory at Arthur Ashe Stadium.
Verdasco, ranked 46th, had won 12 of his 13 previous first-round matches at Flushing Meadows.
Wawrinka, winner of last year's French Open and the 2014 Australian Open, had trailed Verdasco 3-2 in head-to-head action after falling to the Spaniard in straight sets in the first round this year at the Queen's Club run-up to Wimbledon.
"I'm really happy. I think it was a great match, especially for first round," Wawrinka told reporters. "You never expect to play your best game and (be) full of confidence, but I think the level was quite high."
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Wawrinka hit seven winners off his one-hand backhand among his 30 total for the match, blasted in seven aces and turned away all four break points held by the Spaniard.
"Fernando is a tough player to play. He can be really aggressive. He don't give you so much rhythm, so it's not easy," the Swiss said.
"I was really focused on myself. I was moving really well for first one. I'm getting some confidence from that match," added Warwinka, who said he had spent more than a week in New York preparing for the tournament.
"In general, I'm really confident with my preparation, with the way I'm playing in practice court, the way I'm moving."
Despite his close career record against Verdasco, Wawrinka has won both of their grand slam meetings.
"The last few years I have been way better tennis player in the court, especially on big events," he said.
(Editing by Frank Pingue and Mark Lamport-Stokes)
