Del Potro, playing in his first tournament since losing to Novak Djokovic in an epic Wimbledon semi-final, converted four of six break-point chances to win in just under 90 minutes.
After appearing tired and spraying the ball in the first set, Del Potro played near-flawless tennis the rest of the way to dispatch the eighth-seeded Isner, who won in Atlanta last week and was seeking his third title of the year.
Del Potro had trouble returning Isner's missile-like serves early in the match but broke the American twice in the second set and in the opening game of the third.
The Argentine, a three-time winner on the Washington hardcourts and 2009 U.S. Open champion, broke Isner in the seventh game of the final set to take a 5-2 lead and brushed aside three break points in the final game to win the match.
(Editing by Julian Linden)
