FRIBOURG, Switzerland -- First, Mardy Fish put together a compelling rally to get the United States off to a fast start. Then John Isner bashed his way to a big upset.

Now Roger Federer and company are on the ropes.

Isner jolted Federer with his big serve and booming groundstrokes Friday, winning 4-6, 6-3, 7-6 (4), 6-2 to give the U.S. a 2-0 lead against Switzerland in the first round of the Davis Cup.

Isner challenged the 16-time Grand Slam champion in long rallies on the indoor clay court, sending Federer to his first loss in Davis Cup singles in eight years and silencing a Swiss crowd unaccustomed to such outcomes.

"I thought he played great," Federer said. "He played it tough and served great when he had to. I just missed a couple more opportunities than he did and that's what cost me the match."

The 26-year-old Isner called it the "biggest win of my career thus far."

"I'm very proud of it," he said. "I played those break points down very well. It turned the match a little for me."

The upset was preceded by a riveting opening singles match, with Fish outlasting Stanislas Wawrinka 6-2, 4-6, 4-6, 6-1, 9-7.

"Mardy put forth a great effort," Isner said. "That was so gutsy. It took a lot of pressure off of me."

The U.S. can eliminate Switzerland in doubles in the best-of-five series Saturday. Mike Bryan and teenager Ryan Harrison will face Federer and Wawrinka, the 2008 Beijing Olympics gold medalists.

"It's been a difficult day for us," Federer said, adding: "We still have a chance to go through. I'm going to enjoy the challenge."

Before a crowd of 7,000 at Fribourg Forum, Federer started in routine fashion by winning the first set without dropping serve. Isner broke in the sixth game of the second set, but failed to exert any pressure in the third.

Still, the third-ranked Federer couldn't take capitalize on break-point chances in the sixth and eighth games -- winning just one of his 12 opportunities in the match -- and the set drifted into a tiebreaker.

Isner never trailed and clinched on his first set point with a subtle volley at the net that left Federer no chance.

The fourth set turned on the fifth game when Isner rallied from 0-40 down with three big serves and two blistering forehand winners.

Federer never recovered. Isner reeled off four straight games, ending the match by rifling a backhand winner crosscourt.