The top trio were tied on 10-under par, although under the "staggered start" format by which players were spotted strokes based on their position in the playoff standings Thomas needed only to card an even par 70 to land there.
World number one Koepka rattled in a 12-foot birdie putt at 18 to cap a 67 and Schauffele, who won the Tour Championship as a rookie in 2017, posted a 64.
Koepka acknowledged it was "just weird" to arrive at the first tee at East Lake in Atlanta, Georgia, already three shots off the pace. But with one round done the event was feeling more normal.
Thomas topped the standings after his victory in the BMW Championship on Sunday and therefore started the tournament at 10-under, two strokes ahead of Patrick Cantlay, three ahead of Koepka and four ahead of Patrick Reed.
Thomas hit just six of 14 fairways, but he shook off a double-bogey at the par-three 15th - where he was in the water off the tee - to finish strong.
"I'm fine, I'm tied for the lead," Thomas said.
"I thought I played better than I scored today. I played a lot of good golf those last five or six holes - except for that dumb mistake on 15."
Schauffele, who started the day six off the lead, seized the momentum with six birdies in his bogey-free effort and said he tried not to focus on the unorthodox scoring system.
It's designed to ensure the winner of the tournament captures the $15 million FedEx Cup playoff prize.
"I think everyone needed help from JT," said Schauffele, who didn't win the playoff title the year he won the Tour Championship. "If JT went out and shot a pair of 65s I don't think the tour would be very happy and I don't think the rest of the field would be happy.
"But it looks to be a good tournament so far."
Northern Ireland's Rory McIlroy fired a 66 to lie one off the lead at nine-under.
McIlroy made three of his five birdies on the back nine, including a 14-footer at 13, but he couldn't get a seven-foot birdie attempt at 18 to fall.
Matt Kuchar posted a 66 to join Patrick Cantlay (70) on eight-under.
"You kind of look at it more like a five-round tournament," Kuchar said. "The guys came in wherever they were, that was round one of five.
"I was in a position six shots back and you put me six shots back going into Sunday's final round, I feel like I've got a chance.
"You put me six back with 72 holes to go, I've definitely got a chance."
Leading first-round scores on Thursday in the US PGA Tour Championship at East Lake in Atlanta, Georgia (USA unless noted, par 70. Totals to par reflect "staggered start" format):
Xander Schauffele 64
Brooks Koepka 67
Justin Thomas 70
Rory McIlroy (NIR) 66
Matt Kuchar 66
Patrick Cantlay 70
Hideki Matsuyama (JPN) 66
Paul Casey 66
Jon Rahm (ESP) 68
Patrick Reed 70
Adam Scott (AUS) 68
Gary Woodland 68
Im Sung-jae (KOR) 67
Justin Rose (ENG) 68
Corey Conners (CAN) 68
Tony Finau 70