In the final major of the year, Thomas started the day at 5-under and was two shots behind leader Kevin Kisner.
Thomas began his move on the seventh hole, from where he birdied four of the next six holes, including a dramatic putt on the par-5 10th.
Needing an eagle on the tough 18th hole to tie with Thomas, Kisner instead fired his second shot into the stream, handing Thomas the victory.
The son of a club professional, the 24-year-old from Kentucky, who has been in brilliant form on the PGA Tour this year, became the eighth first-time major victor since 2015, finishing two shots clear of a trio including American Patrick Reed, South Africa's Louis Oosthuizen and Italy's Francesco Molinari.
Thomas didn't start the round looking like the eventual victor after making bogeys on two of the first three holes.
Thomas finished two shots ahead of fellow American Patrick Reed, Italy's Francesco Molinari and Louis Oosthuizen of South Africa, who finished tied for second at six-under.
Sharing fifth on five-under were American Patrick Reed, Italy's Francesco Molinari and South African Louis Oosthuizen, the only major victor in the hunt.
Spieth and Fowler were waiting beside the 18th green to embrace Thomas before he signed his card to claim the first prize of 1.89million USA dollars (£1.4million) for his fourth win of a remarkable season.
"I didn't make the putts that I'd been making the first 2 days over the weekend", he said.
Ten years later, they have won consecutive majors and head into the FedEx Cup playoffs battling for PGA Tour player of the year.
"I don't think there's a whole lot out of this other than just execution on the greens, " Spieth said. "I knew I had the game to get it done".
Johnson made seven birdies on the day and shot 32 on the front nine.
Third-round leader Kevin Kisner closed with 74 and was 4 under.
Oosthuizen, the only major victor among the contenders after his 2010 British Open triumph, holed a 34-yard chip shot eagle at the par-5 15th but followed with a bogey to blunt the impact of his closing birdie.
He hooked his approach into the creek and made double bogey, finishing four behind. However, Spieth, who has been close friends with Thomas since they were 14 years old, was at the last green late Sunday afternoon along with Rickie Fowler to watch Thomas make the final putt to win the Wanamaker trophy.
The final three holes at Quail Hollow are known as The Green Mile, and those holes almost ruined Kisner's third round.
Thomas completed a two-shot win with a three-under 68 in the final round on Sunday.
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