Scheffler, this year's Players Championship winner, began on 10-under par at East Lake in Atlanta with a two-stroke lead over Norway's Viktor Hovland thanks to staggered scoring based upon season point totals.
But two-time major winner Morikawa, who began on 1-under and nine strokes adrift of Scheffler, fired a stunning nine-under par 61 to leap within two of fellow American Scheffler, who had seven to play.
"You've got to have your foot on the pedal," Morikawa said. "This is the end of our season for a reason. Even though I had a great round today I want to keep doing that for next few.
"I haven't been this pin-high with my irons in quite some time. That's a sign of control. And then being able to make some putts. I still left some out there but I'm not going to complain at all. I'm very, very pleased with this round."
It was Morikawa's career-low PGA Tour round, one under his final round at last year's Tournament of Champions.
"I've grinded my butt off. I've spent way too much time out there," Morikawa said of practice rounds. "But I figured some things out. It's obviously nice to see."
Asked what was working after firing seven birdies and an eagle in a bogey-free round where he closed with three straight birdies, Morikawa said, "Everything."
It boosts Morikawa's chances of getting a US Ryder Cup captain's pick next week, but that's not at the top of his thoughts.
"I want to win this week. I want to find a way to win," he said. "That would be an awesome goal of mine and let everything else happen. I've got to focus on this week and get it done."
Defending champion McIlroy, a four-time major winner from Northern Ireland who began three adrift on 7-under, answered bogeys on the second and eighth holes with a birdie at 10 but made bogey at 11 as he battled lower back pain.
World number two McIlroy injured a muscle in his lower right back while at home Monday, according to The Golf Channel, which said his back locked up Tuesday and he had not practiced or played since.
McIlroy was considering withdrawing from the 30-player event, according to the report, but after treatment sessions Thursday and hitting 20 balls on the driving range, decided to play the opening round.
McIlroy, who won last month's Scottish Open for his 24th PGA Tour title, had used a new putter the past two weeks but went back to his more regular putter Thursday.
The Tour Championship will award an $18 million playoff bonus prize to the winner.
Morikawa sizzles early
Last year, McIlroy charged from six strokes back in the final round to edge Scheffler for the title in the biggest last-day comeback in event history.
Morikawa, whose last win came at the 2021 DP World Tour Championship in Dubai, collected major wins at the 2020 PGA Championship and 2021 British Open and roared into contention quickly on Thursday.
Morikawa dropped his approach at the first inside three feet and made his birdie putt, sank a 20-foot birdie putt at the fifth then eagled the par-5 sixth after dropping his second shot inside four feet from the hole.
After sinking a 12-foot birdie putt to begin the back nine, Morikawa made a 36-foot birdie putt at the 12th, a 10-footer to birdie 16 and a 13-foot birdie putt at the 17th.
Needing an eagle at the par-5 18th to match Zach Johnson's course record of 60 from the 2007 Tour Championship, Morikawa found a greenside bunker 60 feet from the hole but blasted out to six feet and sank the birdie putt for 61.
Scheffler made an eight-foot birdie putt at the first hole, rolled in a 32-footer for birdie at the fourth and reached the green in two to set up a tap-in birdie at the par-5 sixth, but he stumbled with three-putt bogeys at the eighth and 11th around a birdie at the 10th.
