Roddick converted only two of 13 break-point chances but dominated with his serve, as often happens at Wimbledon, where he's a two-time runner-up.
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"I served really well," he said. "I would have liked to have converted more break points. But I got a couple and, thankfully, that's all I needed."
The Olympic match, delayed a day by rain, was Roddick's first in eight years. He lost in the third round at the 2004 Games and skipped Beijing in 2008.
As a price for being unseeded, he'll face a daunting challenge in the second round: Novak Djokovic, the 2011 Wimbledon champion.
"The guy has been the best player in the world over the last couple of years," Roddick said. "It's going to be tough. But the situation, we've both been through it a million times. I'm going to have to serve well and take some chances on returns."
Isner, seeded 10th, lost only 16 points in his 11 service games. The victory came on Court 1, the first time Isner has played in one of Wimbledon's two largest stadiums.[+] EnlargeKyle Terada/US PresswireAndy Roddick won his first-round match over Martin Klizan, 7-5, 6-4 at Wimbledon Monday.
Routine wins have been elusive at the Olympics for Federer, who is playing in the Games for the fourth time and still seeking his first singles medal. He was pushed to three sets in the opening round but he easily eliminated Benneteau, who held a two-set lead against Federer at Wimbledon a month ago before losing.
In the rematch, Federer lost only 13 points in his eight service games. He had 24 winners and only seven unforced errors.
Lleyton Hewitt of Australia and Nikolay Davydenko of Russia, both three-time Olympians, won their opening matches. No. 9-seeded Juan Monaco of Argentina, No. 13 Marin Cilic of Croatia, No. 16 Richard Gasquet of France and big-serving Milos Raonic of Canada, also advanced.
Roddick, a dedicated Davis Cup player for the United States, took Court 2 on a sunny morning looking particularly patriotic. He wore a blue shirt, white shorts and stars-and-stripes shoes.
"Posh sneakers, Andy," shouted a spectator with a British accent.
Roddick had the bulk of the crowd support, although a chant of "U-S-A! U-S-A!" quickly fizzled.
He lost only nine points in 11 service games, and the first break point came on the final shot of the opening set, which put him ahead to stay.
Roddick won with more than just his serve, hitting several improbable shots, including a back-to-the-net lob to help win one point, and a backhand as he did a belly flop behind the baseline.
Information from The Associated Press was used in this report.
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