US star Scheffler made seven birdies against a lone bogey to shoot a six-under par 64 while England's Fitzpatrick had five birdies before a controversial closing bogey left him on 66 at Olympia Fields in suburban Chicago.
That left them on 11-under 199 after 54 holes in the penultimate FedEx Cup playoff event, where the top 30 in season points advance to next week's Tour Championship in Atlanta.
"I played what felt like a great round," Scheffler said. "The winds were shifting around a bunch out there... but I did a good job of when I got into trouble, got out, and my short game was really nice."
American Brian Harman, last month's British Open winner, was third on 200 after a 67 with countryman Max Homa, who set the course record Friday with a PGA career-low 62, fourth on 201 after a 71.
Reigning FedEx Cup champion Rory McIlroy, a four-time major winner from Northern Ireland, fired 67 to share fifth on 201 with Norway's Viktor Hovland, who shot 65.
Fitzpatrick, leading by a stroke, saved par from a greenside bunker at 17 but at 18 found a fairway bunker and the left rough, where he said a course marshal "semi-stood" on the ball.
"Didn't fully stand on it, but definitely brushed it because you could see the grass was completely moved," Fitzpatrick said.
"It was definitely sat further down than when I got there. They didn't see it, and they can't confirm that, so I wasn't going to fight for it, really."
Instead, he punched into the fairway and went up and down for bogey to fall back level with Scheffler, saying his third shot was impacted.
"Not a different angle, but it just came out heavy," Fitzpatrick said. "If it sat up a little bit lighter, it comes out a little bit better on the green - it's a little less stressful bogey than what I had."
It was a tricky day for leaders.
Homa birdied the second and fourth holes to stretch his lead but was undone by a triple bogey at the seventh - needing four to reach the green and three-putting from 13 feet.
When Harman made bogey at the ninth despite finding a fairway bunker, he fell into a three-way shared lead with Homa and Fitzpatrick.
Harman birdied 10 to grab the lead, but 2022 Masters winner Scheffler, this year's Players Championship winner, began the back nine with three birdies, the last and longest from 13 feet, to match him on 10-under.
That's when Fitzpatrick charged, sinking a 14-foot birdie putt at the par-3 13th, a 21-footer at 14 and a four-footer at the par-5 15th after a great rescue shot from left trees to retake the lead after Scheffler birdied 15.
McIlroy stalls
McIlroy, who can overtake Scheffler for number one with a victory, made four birdies in the first six holes but stumbled with bogeys at nine and 10 and ended four adrift.
"Got off to a great start, holed some nice putts early, sort of stalled in the middle of the round," McIlroy said. "I could have been a couple closer to the lead but overall happy with how I played."
American Sam Burns matched Homa's day-old course record with a bogey-free 62 to stand on 203.
"I just want to go out there and play with confidence, play free and see what happens," Burns said.
American Lucas Glover, the 2009 US Open champion who won PGA titles the past two weeks, was seven adrift after a 69.
Fourth-ranked American Patrick Cantlay, the two-time defending BMW champion, fired 71 to stand on 207.
The BMW is the final US qualifying event for next month's Ryder Cup, with six spots to be decided on points Sunday.
