Australian Min Woo Lee matched Scheffler's three-under-par 67 to also sit in a record-setting seven-way tie atop the leaderboard at Aronimink Golf Club outside of Philadelphia.
That crowded leaderboard is a cosmopolitan one with big-hitting South African Aldrich Potgieter, Japan's Ryo Hisatsune, Germans Stephan Jaeger and two-time major winner Martin Kaymer, and Scheffler's fellow American Alex Smalley also firing 67s.
But the sight of Scheffler spells trouble for his rivals at a tournament where the cream almost inevitably rises to the top come Sunday.
Scheffler is only the third defending champ and world No.1 to lead or co-lead after round one. The others were Tiger Woods in 2007 and Brooks Koepka in 2019 - and they both won.
The winners of 11 of the past 12 PGA Championships have also been ranked one or two in the world at some point before or after their victory.
And the last nine PGA Championships have been won by a player who today has multiple major championships on his resume - Justin Thomas, Koepka, Collin Morikawa, Phil Mickelson, Xander Schauffele and Scheffler.
There would have been eight frontrunners had South African Garrick Higgo not copped a two-shot penalty for arriving seconds late for his 7.18am tee time.
Higgo argued the toss with officials after signing for a one-under 69, which included a "double-bogey" six at the first.
"It wasn't a surprise. I was late. I mean, my caddie was yelling at me to get to the tee," Higgo said.
"I knew it was probably going to happen, yeah. I was there at 7:18, 30 seconds."
Another seven players, including Schauffele, are just one stroke off the pace.
Australians Jason Day and Cameron Smith, ex-winners Koepka, Justin Thomas, Collin Morikawa and former world No.1s Jon Rahm and the grand slam-chasing Jordan Spieth are among 19 players at one under, just two back, on the tightest first-round leaderboard in major championship history.
But Rory McIlroy fell foul of the huge, undulating and fast greens, the back-to-back Masters champion and world No.2 opening with a deflating four-over 74.
McIlroy bogeyed the last four holes for the first time at a major.
Starting his round from the 10th hole, McIlroy opened with a bogey after having to hack out of the rough, but bounced straight back with a birdie at the 11th.
From there, it was a run of 10-straight pars for the Northern Irishman, who is chasing a seventh major title which would take him past Nick Faldo's tally and make him the most successful European of the modern era.
The two-time PGA champion could not find the spark and he showed his frustration as a sloppy drive on the fourth resulted in a second bogey.
Again, he hit straight back by sinking a 31-foot putt before unravelling coming home.
"Shit," McIlroy said, summing up his round of wayward drives.
But no-one struggled quite like Bryson DeChambeau, the 2024 and 2025 runner-up who didn't make a birdie until he ended on the par-5 ninth hole.
That kept him from matching his highest score in a PGA Championship. He shot 76 and now has to work toward avoiding a second-straight missed cut in a major.
