The tournament's top four seeds all won their quarterfinal matches, with Isner, seeded third, serving 21 aces while downing David Goffin 7-6 (7-5), 6-3. Isner will face No. 1 seed Jo-Wilfried Tsonga in the semifinals, after Tsonga disposed of Marcel Granollers 6-1, 6-2.
Tsonga recently reached the semifinals at Wimbledon before falling to Andy Murray and then got to the quarterfinals at the Olympics before suffering a loss to Novak Djokovic.
The other semifinal Friday will send No. 2 Tomas Berdych against fourth-seeded Sam Querrey.
Berdych had to rally before downing Steve Darcis 4-6, 6-2, 6-0 and Querrey survived a third-set tiebreak in ousting Alexandr Dolgopolov 7-5, 4-6, 7-6 (7-3).
Isner and Tsonga have met three times in their careers, with Isner holding a 2-1 edge. He defeated Tsonga this year in a Davis Cup match.
It will be the fourth finals appearance for Isner this season. He has one tournament title to his credit this year, that coming in Newport, R.I.