Playing on a sponsor exemption in only his third career PGA start and first as a professional, the 23-year-old former college star at Wake Forest fired a closing five-under par 66 to finish 72 holes on 22-under 262 at Black Desert Resort in Ivins, Utah.
That was enough to defeat Rico Hoey of the Philippines by four strokes and take a $1.08 million (£800,000) top prize from the $6 million (£4.5m) purse.
"It's an amazing feeling," Brennan said. "Winning golf tournaments is one of the better feelings in the world. It takes a lot to play professional golf.
"Mental fortitude or focus has gotten a lot better. Definitely have been a lot of technical things that have improved, around the green and on the green, and I think that showed this week."
A third-place pack on 268 included Dane Thorbjorn Olesen, Canada's Ben Silverman and Americans David Ford, Pierceson Coody, Justin Lower and 2024 Utah winner Matt McCarty.
Brennan became the second PGA Tour winner in as many seasons on a sponsor exemption, the first since Nick Dunlap at last year's American Express event in the California desert.
After firing a 64 Saturday to seize a two-stroke lead, Brennan sizzled at the start Sunday with a three-foot birdie on the second hole and a six-footer at the third.
He added a 12-foot birdie putt at the fifth and tap-in birdies at the par-five seventh and ninth holes after reaching the greens in two.
A bogey at the 10th after finding a fairway bunker left Brennan on 21-under, three ahead of Hoey, who sank a 21-foot birdie putt at 12 only for Brennan to birdie as well from just inside three feet.
Brennan drove the green at 14 and sank a three-foot birdie putt to stretch his lead and Hoey stumbled with a bogey at 16 to leave the American ahead by five.
At the par-five 18th, Brennan took an unplayable lie drop and penalty after his second shot landed in a deep hole, chipping onto the green. He just missed an 18-foot par putt then tapped in for bogey and the victory.
Only three events remain for players to try and earn a spot in the top 100 on the PGA Tour season points list and claim full tour rights for the 2026 campaign.