Isner posted a 4-6, 6-3, 6-4 victory over the French qualifier.
Isner, a native of nearby Greensboro, N.C., reached the finals after easing past the struggling former world No. 1 Andy Roddick 7-6 (9-7), 6-4 in one of the Friday's semifinals.
Benneteau reached the title match by rallying past No. 10 seed Robin Haase of the Netherlands, 3-6, 7-6 (9-7), 7-6 (8-6) in the day's other semifinal.
The Frenchman slipped to 0-5 in career finals with the disappointing loss.