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," he added.
Isner had been bidding for his second title of the season after winning in Auckland earlier this year, and looked to have the momentum after claiming the first set. 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.
Meanwhile, Rohan Bopanna’s brilliant doubles run came to a stuttering halt, going down in a hard-fought final with partner Kristof Vliegen.
The Indo-Belgian pair lost to American duo Scott Lipsky and Rajeev Ram 3-6, 7-6 (7-4), 10-12.