The crowd responded with a collective "aww," Isner grimaced and Federer offered a sheepish wave of apology. But after all these years, he's probably overdue for a little luck in the Olympics.
Federer advanced Thursday to the semifinals by beating Isner 6-4, 7-6 (5). With that tall hurdle cleared, four-time Olympian Federer needs one more win to clinch the first singles medal of his career, which would plug the biggest hole in a resume that includes a record 17 Grand Slam titles.
"Being in the medal matches, at least I'll get two shots," Federer said. "That's why I looked at this match as a final. You can imagine the relief and happiness I feel right now."
On Friday, Federer will face No. 8-seeded Juan Martin del Potro of Argentina.
The other men's semifinal will match No. 2-seeded Novak Djokovic of Serbia against No. 3 Andy Murray of Britain. Murray was runner-up to Federer at Wimbledon last month, while Djokovic won Wimbledon in 2011 and was a bronze medalist in Beijing in 2008.
Del Potro advanced by beating No. 15 Kei Nishikori of Japan 6-4, 7-6 (4).
Americans Bob and Mike Bryan advanced to doubles semifinals by edging Jonathan Erlich and Andy Ram of Israel, 7-6 (4), 7-6 (10). Neither team managed a service break, and the Bryans sealed the victory on their fourth match point when Erlich double-faulted into the net.
On a sunny, gusty afternoon on Centre Court, Federer's victory swung on just a few points. Both players went for quick strikes, which meant short rallies and less than scintillating tennis for the capacity crowd.
Midway through the second set, the chair umpire yawned.
Isner hung tough playing on Centre Court for the first time, and the close score did produce some tense moments, the last coming on the final point. The big American hit a 137 mph serve, and Federer lined a backhand return that caught the net and still landed a winner.
"You just feel bad, really -- but relief, because it's finally over," Federer said.
"It goes against you sometimes; it goes for you sometimes," Isner said. "It's unfortunate, but I'm not going to dwell on it. He was better than me today."
Federer recalled winning a match the same way against Ivan Ljubicic in a Key Biscayne final.
"I actually texted him to tell him the same thing happened again," Federer said with a chuckle.
Federer was also fortunate to take the lead for good in the ninth game when Isner blew a forehand sitter. Isner then stomped his chair chewing on his shirt, sat and buried his head in a towel.
That point, which put Federer ahead 5-4, resulted in the only service break of the match.
"Maybe I just got really lucky today," he said. "But overall I felt I played a great match. ... I think I'm playing my best. I don't know if you can play a whole lot better."
Information from The Associated Press was used in this report.