Thomas trailed by seven shots heading into the final round but produced a battling display on Sunday, recovering from a slow start to fire a closing 67 courtesy of birdies at the 11th, 12th and 17th.
Although he missed an 11-foot birdie putt at the last, his five-under-par total was enough to get him into a three-hole aggregate play-off with Zalatoris after the one-shot lead Mito Pereira took to the 18th evaporated due to a double-bogey at the last.
Thomas held his nerve to match Zalatoris' birdie at the opening play-off hole - the 13th - before finding the green with his tee-shot at the par-four 17th.
He sent his lengthy eagle putt to within a few feet, and after watching Zalatoris miss his birdie effort, Thomas rolled in for a three to take a one-shot advantage to the 18th tee.
With Zalatoris failing to make a birdie at the third play-off hole, Thomas settled for a two-putt par to claim the Wanamaker Trophy for the second time and become a two-time Major Champion.
Thomas said: "It hasn't sunk in just yet. I think it did more in the moment. I was jittery and I almost kind of couldn't feel my limbs walking up to that tap-in.
"Although trying to two-putt from 25 feet or whatever it was is usually pretty doable, but downhill when you know you've got a two-putter to win, I was very pleased to see it end up that close to the hole."
The 29-year-old, who won this tournament at Quail Hollow in 2017, felt his experience helped him get over the line.
He added: "I played that back nine beautifully. The holes I didn't make birdie or have birdie putts I had really good looks, and I hit great putts that just didn't go in, and the holes I missed the green I was able to salvage a par, which is what you have to do to win a Major.
"I kept telling myself I've been here before. Although it's been five years, it's somewhere down in there."
Thomas mixed two birdies with two bogeys on the front nine on Sunday, before his round sprung to life when he holed an enormous birdie putt at the 11th and followed that up with another gain on the 12th.
Another birdie arrived at the 17th, much to the delight of the huge crowds in Tulsa, but Thomas could not convert his birdie chance on the 18th green.
It had looked as though Thomas' five-under-par total - which was matched by Zalatoris after he nervelessly holed his par putt from eight feet at the 18th to sign for a 71 - would not be enough as Pereira, playing in the final group, took a one-shot lead to the last.
But the Chilean, who began the day with a three-shot lead and was never knocked off the summit until the very last hole on Sunday, sent his tee-shot into the water and failed to make the bogey which would have earned him a spot in the play-off.
Pereira finished in a tie for third on four under par alongside American Cameron Young, while Matt Fitzpatrick, Tommy Fleetwood and Chris Kirk were another shot further back.
Zalatoris was proud of his second-placed finish. He said: "I'm obviously pretty proud to be sitting in this position considering on Saturday, I never thought I would have been standing here.
"I always felt like I was one, two, three back and then once I saw Mito hit in the water on 18, I knew that putt that I was going to have on 18 was probably to get into a play-off. So I will bottle that putt on 18 for the future."