Lopez outlasted the second-seeded Frenchman in the Wimbledon grass-court tuneup 7-6 (7-2), 6-7 (5-7), 6-0.
Simon battled back from 1-4 to win the second set, but Lopez prevailed in a third set that was more competitive than the 6-0 score indicated. Lopez fired 16 aces versus four for Simon.
The match lasted nearly 3 hours in the blustery conditions in Eastbrooke.
Lopez, who won his first title since 2010, will face Simon again in the first round at Wimbledon, which begins Monday.