Fitzpatrick was part of the European team that lost to the US by a record 19-9 margin at Whistling Straits and failed to record a point, having also blanked on his debut five years previously.
But he showed no ill effects after a two-week break, carding a closing bogey-free 69 to finish at six under and hold off the challenge of Swede Sebastian Soderberg and Australia’s Min Woo Lee.
Fitzpatrick started the day three shots off the lead but 15 consecutive pars were enough to edge him closer to the top of the leaderboard at the notoriously difficult 1997 Ryder Cup venue.
Soberberg had made a big move through the field, picking up four shots in his first four holes with the help of an eagle on the fourth and led by two at six under with two to play.
But the 31-year-old lost his ball off the tee at the 17th and Fitzpatrick was able to pounce, making his first birdie of the day from 10 feet on the 16th to take the lead.
He two-putted from over the back of the par-five 17th for a second birdie in a row and, with Soderberg also bogeying the last in a closing 70, it was a seventh win in as many seasons on the European Tour for the man from Sheffield.
“Winning around Valderrama is something you want to tick off on the bucket list,” he said. “To do it in the way that I did, with no bogeys in the final round was extra special.
“I felt if I could hang in there, hang around and pick up a couple of birdies if possible, pars were never a bad thing, and that’s what I did.
“You can hit half decent shots and be behind a tree and you’re chipping out or you’ve got to manoeuvre something, it’s a true test and to be patient the whole 72 holes, I’m really pleased with the way my attitude was all week.”
Lee carded a 70 to share second with Soderberg, a shot clear of a group containing Englishmen Laurie Canter, James Morrison and Robert Rock.
Canter had entered the day with a three-shot lead but carded a closing 76, eight shots more than Morrison, while Rock signed for a 69.
Additional reporting by PA.