The 32-year-old Belgian took advantage of ideal conditions and navigated the rowdiness at the tour's most boisterous tournament to enter the final round with a five-shot lead.
World No.1 Scottie Scheffler, Jordan Spieth and Daniel Berger all made Sunday charges, but Detry hit it to 16 inches on 16 to seal his first win in 68 PGA Tour starts.
Detry added two more birdies to finish at 24-under 260, becoming the first Belgian to win on the PGA Tour.
Berger shot 67 and tied for second with Michael Kim (67) at 17 under. Spieth shot 68 to tie for fourth at 16 under with South Africa's Christian Bezuidenhout (66).
Justin Thomas holed out from 103 yards for eagle on 18 to shoot 65, finishing tied for sixth.
Lone Australian Min Woo Lee eagled the par 5 13th on his way to a 67 as he tied for 12th, 11 shots behind Detry.
Detry had been waiting for this moment.
He won the European tour's Bridgestone Challenge in 2016, twice represented Belgium at the Olympics and had two runner-up finishes on the PGA Tour - most recently at the 2024 Houston Open.
All that was missing was a PGA Tour win.
Detry put himself in position with stellar ball-striking and putting in the desert.
He entered the final round at 18 under, shot one-under 34 on the front nine and still had a four-shot lead heading to the back.
He reached 20 under with a birdie on the hardest hole on the course, the 470-yard, par-4 11th, and added a two-putt birdie on 15 before his near-ace on 16.
"This course, there are birdies out there, but once you start missing fairways, those tricky pin positions and the firm greens, the course can bite you," Detry said.
"So I was able to trust my game and kind of rely on that."Several players put pressure on Detry as they climbed the leaderboard.
Berger made the latest charge. He briefly cut into the lead with a birdie on the par-5 15th, but Detry poured in one on top of his to keep the margin at three.
Berger bogeyed No. 16 after bouncing his tee shot through the green, ending his comeback bid.
Spieth shot 33 on the front to get to 15 under, but had just one birdie over his final 11 holes.
Scheffler shot 31 on the front nine to reach 14 under, but he had three bogeys and a double bogey coming home to finish with a 72 and plunge to tied 25th.
