Schauffele put the finishing touches on a wire-to-wire victory at the year's second major with a closing six-under-par 65 that left him at 21 under on the week.
Needing a closing birdie for the win, Schauffele's tee shot at the 18th perched up on the edge of a fairway bunker and forced him to take a compromised stance inside the hazard for his second shot, which he left just in front of the green.
Schauffele then displayed nerves of steel as he chipped to six feet from where he drained the biggest birdie of his career for the lowest winning score to par at a major championship.
"I really didn't want to go into a playoff against Bryson," Olympic champion Schauffele said. "I'm assuming we probably would have played 18. It would have been a lot of work. I just told myself, this is my opportunity, and just capture it."
DeChambeau carded a bogey-free seven-under-par 64 to finish two shots ahead of Viktor Hovland (66), whose spirited effort to become the first Norwegian to win a major came undone at the final hole.
DeChambeau and Hovland were playing in the third-to-last pairing and set up pressure-packed 10-foot birdie putts on the final hole. DeChambeau drained his but Hovland's effort curled away and he went on to make bogey and finish third.
That left the outcome in the hands of Schauffele, who was playing the par-four 17th where he did well to save par after his tee shot caught a fairway bunker before sealing the deal at the 18th while DeChambeau watched it unfold on a nearby screen.
DeChambeau handled the defeat with the utmost class as the 2020 US Open champion, who had been warming up in anticipation of going to a three-hole aggregate score playoff, took time to find Schauffele and congratulate him.
"It's cool to see him - not only he's just a great human being, but an unbelievable golfer, and it shows this week. Super happy for him," said DeChambeau.
"On my side of the coin, disappointing, but, whatever. I played well. Didn't strike it my best all week. Felt like I had my 'B' game pretty much."
Three-horse race
A day that began with seven players within four strokes of overnight co-leaders Schauffele and Collin Morikawa (71) turned into a thrilling three-horse race across the back nine.
Schauffele reached the turn clinging to a two-shot lead that vanished by the time he walked off the 10th green where his par putt lipped out shortly after Hovland, playing two groups ahead, birdied the par-four 12th.
Hovland then poured in a 15-foot putt right into the centre of the cup at the par-four 13th for his third birdie in a four-hole stretch to snatch the outright lead from Schauffele.
But a determined Schauffele, unfazed by his bogey, refused to back down from the challenge and flashed his resolve, hitting right back with birdies at the 11th and 12th holes to regain the outright lead before going on to close the deal.
DeChambeau might not have even been in contention if not for a fortunate break at the par-four 16th where his tee shot was headed for a steep bank of thick rough before it bounced off a tree and into the fairway.
DeChambeau took full advantage with a brilliant approach shot from 219 yards out that settled three feet from the cup from where he made birdie to get within one.
"Thank you to the tree," a laughing DeChambeau said. "You got to have breaks like that happen. I fully took advantage of that second shot, put it in there close, hit a great shot."
Scheffler tired
Scottie Scheffler, who was arrested outside Valhalla ahead of Friday's second round following an incident with police, began eight shots back of the leaders and finished with a six-under-par 65 that was his lowest round of the week.
It was an impressive response from Scheffler a day after his par-or-better streak ended at 42 rounds but ultimately proved too little, too late in his bid for a fifth win in six starts.
"I'm trying to figure out how quickly I can get home from here and, yeah, that's pretty much it," said Scheffler. "I think I'm just fairly tired and ready to get home."
Defending champion Brooks Koepka, who began the day 11 shots behind the co-leaders, had five birdies through his first 12 holes en route to a five-under-par 66.
"Not very good," LIV Golf's Koepka said when asked to assess a week where he was looking to become the PGA Championship's first repeat winner since he retained the title in 2019. "I think it's pretty obvious, isn't it."
Jordan Spieth, who began the day seven shots off the lead and with an outside chance of completing the career Grand Slam of golf's four majors, closed with a 73.
Northern Irishman Rory McIlroy, who has been stuck at four majors since his 2014 PGA Championship triumph at Valhalla, began his day seven shots back of the co-leaders and settled for a share of 12th after a four-under-par 67.
