The Argentine prevailed over Isner 6-2, 3-6, 6-3 to claim his fifth career ATP Tour title.
He survived eight aces fired by his second-seeded opponent en route to the victory.
Isner, meanwhile, continued a streak of American players reaching the Houston finals in 11 of the past 12 years.
Notable deaths of 2014 [PHOTOS]
Michael Sam cut from the Dallas Cowboys