Fognini, a 31-year-old Italian ranked 15th in the world, won the hard-court event for his third victory of the year and eighth overall. He also won clay-court titles this year in Bastad and Sao Paulo.
Fognini lost the first three games against del Potro, then won 12 of the last 15.
Del Potro, ranked No. 4 in the world, missed a chance to win in his first event since a five-set loss to Rafael Nadal in the Wimbledon quarterfinals. The 2009 U.S. Open champion has 22 victories, winning this year on hard courts at Indian Wells and Acapulco.