As Australians Adam Scott and Min Woo Lee enhanced their prospects of qualifying for the $US40 million ($A56.5 million) season-ending Tour Championship, Scheffler converted a two-shot third-round lead into an eight-stroke procession in Memphis, Tennessee.
Scheffler closed with an authoritative four-under-par 66 to leave his would-be chasers in his wake with the largest winning margin in the 68-year history at the TPC Southwind on Sunday (Monday AEST).
The four-time major champion finished at 17 under to capture his 21st PGA Tour title and end a frustrating drought stretching back to January.
Scheffler had been runner-up five times and posted five other top-four showings since winning the American Express in the Californian desert on Australia Day.
"I was like, 'man, when is this going to stop happening?'" Scheffler said.
But there was no denying the 30-year-old American this time as he collected not only the $US3.6 million ($A5.1 million) winner's cheque but also an additional $US23 million ($A33 million) in bonus money for being No.1 in the season standings through to next week's BMW Championship.
No one can catch him.
Even after dropping a shot at the par-5 third to allow Sungjae Im to pull within one shot of the lead, Scheffler still managed to street his rivals after putting the foot down with five birdies in a 12-hole stretch.
South Korean Si Woo Kim (68) snared the runner-up spoils at nine under, with American Sam Burns (73) and Swede Alex Noren (69) sharing third one stroke further back.
After starting the day equal second with Burns, Im (74) had to settle for joint fifth at seven under with dual US Open champion Wyndham Clark (68), some 10 shots behind Scheffler.
"I've have some close calls this year. It is always challenging playing with one of my best friends but going into today I wanted to do my best," Scheffler said.
"I've been really consistent. That's what I'm most proud of. It's nice for it to pay off this week. This is a lot better feeling than having a statistically-good week."
Scott's final-round 70 left him in a tie for 12th at five under, nudging the former world No.1 from 29th to 27th in the season-long FedExCup standings.
Only the top 30 players will make it to Atlanta for the season finale from August 27-30.
The top 50 after Sunday's first play-off event advance to the BMW Championship, where Scott and Lee will have the chance to book their tickets to East Lake.
Lee closed with a 71 to wind up in equal 55th at four over to drop from 17th to 18th in the points race, but still comfortably on track for a first-time appearance at the the Tour Championship.
The 28-year-old has never even reached the penultimate event of the season before but progressed to the BMW Championship after four top-10s this season, including two runner-up efforts.
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