Scott started the day two shots off the lead heading into the final round in a five-man group, but 2025 US Open champion Spaun struck form just when it mattered with four birdies in his last five holes to seal a dramatic win on his debut.
It meant the American's final-round 67 saw him finish two shots clear of a group of four players on Sunday, including 46-year-old Scott, Rory McIlroy, Aaron Rai and Manuel Elvira who all tied for second place.
Elvira eagled the 17th to join Spaun at the top of the leaderboard but the Spaniard suffered a double bogey on the last which ultimately handed the win to the American, who admitted the disappointment of being left off the Presidents Cup team had fired him up.
"I played with a huge chip on my shoulder," Spaun said of being overlooked as a captain's pick for the Cup next week outside Chicago.
"I definitely had something to prove this week, but everything happens for a reason. I'm so delighted to be here and just play this event. The extra motivation, I think that is the willpower that you kind of have, determination.
"Being left off the Presidents Cup team a couple of weeks ago was very disappointing and I wanted to prove that I deserved to be on that team. I took care of my business this week, so all the best to my mates next week at Medinah, but I'll be on the couch watching."
Scott, who bettered his third round score of 71 by three shots on Sunday, finished on 15 under 273 for the tournament with McIlroy also carding a final round 68.
The Northern Irishman found a bunker from his drive on the 18th, was forced to lay up and missed an eight-foot birdie chance.
"I had my chances out there," McIlroy said.
"I wish I had some of those putts back, but I have to be encouraged with where my game is at."
Spaun's rich run of form has now produced four career wins, three in the last 15 months.
"I blossomed into this player I never thought I could be," he said.
"I've always wanted to be a global player. I'm really happy my schedule worked out the way it did."
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