Fish, who won the Hall of Fame Championships in Newport two weeks ago, extended his winning streak to 10 matches after dominating the third-set tiebreak.
"This is as top as I've ever been," Fish told reporters. "I've never won two tournaments in one year, I've never won two tournaments in a row, and on the ATP tour, I've never won 10 matches in a row. It's probably as good as it's been."
But Fish responded with a break late in the second and again early in the third.
Isner broke back immediately in the decider and threatened to break his fellow American again in the ninth game, but fell short and ended up conceding a decisive 4-0 lead in the tiebreak.
Fish, appearing in his third final in his past four tournaments, mowed through the final three points to complete victory and continue his brilliant run.
(Reporting by Mike Mouat in Windsor, Ontario. Editing by Ian Ransom)