Top seed and defending champion Isner advanced to the quarterfinals at the Hall of Fame Tennis championships on Wednesday, beating France's Mahut 6-2, 7-6 (2).
The win by Isner featured the two players that played the longest match in tennis history.
Two years ago, the pair played 11 hours, 5 minutes at Wimbledon, with Isner finally getting a 70-68 fifth-set victory.
This one didn't have nearly the drama with the 6-foot-9 Isner using his overpowering serve to take charge. It ended when Mahut double faulted, ending the match in 1 hour, 18 minutes.
Last year, the pair met again at Wimbledon, with Isner winning in three sets in a match that lasted about two hours.
On Wednesday, playing under bright and sunny, late-afternoon skies with a slight breeze and a larger than usual crowd for the time of day, Isner ousted Mahut on Newport's grass court.
''From the moment I warmed up today I knew I was going to play better,'' said Isner, who struggled in his opening-round match Tuesday. ''Getting that first match over yesterday helped a lot - even though it wasn't the prettiest of matches.''
He broke in the first game of the match and again in the third en route to a 4-0 lead. He closed the first set in 31 minutes, getting aces on the final three points.
''If I serve well it makes a big difference in my matches - no matter how I'm playing in the other facets of the game,'' he said. ''That's a weapon that I'm very fortunate to have.''
And that ended a rematch of the pair that played on three different days two years ago.
''Next year's Wimbledon we'll probably see each other,'' he said, smiling when his news conference ended.
Isner had 13 aces in the match.
Second seed and Japan's Kei Nishikori also advanced to the quarterfinals, outlasting Olivier Rochus from Belgium 6-7 (6), 6-4, 6-2 in a match that lasted nearly two hours.
Nishikori, ranked 18th in the world and the highest in his country, held a 5-0 lead in the tiebreak before losing the first set. He threw his racket to the ground twice as he headed to his chair for a break.
''It's always tough when you have set point and you lose the set,'' he said. ''I just tried to forget the first set and concentrate on each game. Luckily I got a break in the third game. I was able to keep my fight going.''
In other second-round play, Dudi Sela of Israel beat American Sam Querrey, a 2009 Newport runner-up who is recovering from an elbow injury last year 5-7, 7-6 (6), 6-2.
Querrey was up 5-3 in the second set and had two match points before Sela rallied.
Rajeev Ram, the 2009 Newport champion, beat fellow American Michael Russell 7-6 (8), 6-3; and Izak Van Der Merwe of South Africa beat American Jack Sock 6-4, 6-4.
Wild card and former No. 1 in the world Lleyton Hewitt of Australia beat American qualifier Tim Smyczek 6-4, 2-6, 6-1.
- John Isner
- Nicolas Mahut