He described the victory as life-changing after carding a closing 67 to finish at 14-under-par 266, edging fellow American Robert Streb by one stroke.
Another American, Jamie Lovemark, and Colombian third round leader Sebastian Munoz finished two behind.
All four players qualified for the British Open at Royal Birkdale in two weeks.
Davis Love, 53, seeking to became the oldest winner on tour, faded with a 75 after starting the day four strokes off the pace.
For much of the back nine on Sunday it looked like nobody wanted to win, as the four contenders, with only one victory between them on tour, stumbled one after another, before Schauffele came through with two birdies in the final three holes for his maiden triumph.
Schauffele, 23, said his self-belief was boosted by a tie for fifth at the U.S. Open three weeks ago.
“The U.S. Open was a huge moment in my career,” he told reporters. “It kind of gave me the confidence and allowed me to play and win this week.”
Not that he did not have his nervous moments on Sunday in what was only his 23rd start on tour.
“I felt very nervous kind of late in the round. I tried to back to the basics, close my eyes and take some deep breaths.”
Schauffele comes from strong sporting stock. His father Stefan was a promising decathlete whose international dreams were dashed when he suffered a serious eye injury in a car crash.
Stefan subsequently moved to the United States and married a woman from Taiwan, the couple settling in southern California.
Schauffele acknowledged the role of his father in his development.
“He kind of put me on some plan of his and I would say we’re trending,” he said.
“It’s slowly sinking in. I had a couple minutes to myself in the locker room, but it’s just been an incredible feeling and it’s honestly just a dream come true.”
(Reporting by Andrew Both in Cary, North Carolina; Editing by Ken Ferris/Peter Rutherford)