The third seed survived three match points before beating his second-seeded Czech opponent.
The big serving American fired 22 aces in the match but he recived a large slice of luck on the penultamte point as a Berdych forehand hit a net cord and went out.
Berdych slammed a racket to the ground in frustration after the match after failing on all three of his match points in the tie-break including one on his own serve while 6-5 in front.
It was the fifth ATP title of Isner's career and his second in 2012. He also defended his title in Newport in July.