Oklahoma coach Lon Kruger didn't like the outcome, but he has no regrets about taking his 18th-ranked team on the road to play Creighton.
The Sooners built an 18-point lead early in the second half, but they squandered it and lost 65-63.
"As far as learning opportunities," Kruger said, "there are a lot of them in a game like this. A crowd like that, you can't simulate that, so that part is good. The experience we'll get from this is good."
After Jordan Woodard missed his desperation 3-pointer at the buzzer, the CenturyLink Center sellout crowd of 17,393 roared and Creighton's student section came pouring onto the floor.
"This loss should bring us together even more," said Buddy Hield, who led the Sooners with 21 points. "We can't be comfortable with a lead. We'll build off that and learn."
The Sooners (1-1), who returned their top three scorers from a 23-win team, for a half looked like they would overpower a Creighton team that lost Doug McDermott, the 2014 national player of the year, and three other seniors.
Oklahoma led 35-24 at halftime after Creighton came out shooting 24 percent (6 of 25). The Bluejays' turnaround was sudden. Isiah Zierden and Chatman hit 3-pointers to ignite the 24-4 run that swung the game.
"They got a couple shots in transition and sparked the crowd," Hield said. "They feed off their crowd. Their crowd helps them a lot. The noise in the building sped us up a little bit, and we have to be grown men and settle ourselves down and execute our plays down the line."
Zach Hanson scored the go-ahead points, catching Devin Brooks' air ball along the baseline and putting it in the basket with 49 seconds left.
Austin Chatman, who had 17 points, hit a couple of free throws to make it a four-point game with 24 seconds left. But Oklahoma still had a chance after Brooks missed three free throws in the last 14 seconds.
Toby Hegner and Isaiah Zierden added 11 points apiece for Creighton (3-0).
TaShawn Thomas added 14 and Ryan Spangler had 11 for the Sooners, who shot 30 percent in the second half and 35.5 percent for the game. They committed seven of their 12 turnovers after half.
For Creighton, which is picked to finish ninth in the 10-team Big East, the 18-point deficit was the biggest overcome in a win in coach Greg McDermott's five seasons at Creighton.
Oklahoma: Hield, who set a school record and tied the Big 12 mark for most 3-pointers in a game without a miss by going 7 for 7 against Southeastern Louisiana, made his first 3 against Creighton before missing for the first time this season.
Creighton: Toby Hegner drew a roar from the crowd late in the first half when he bumped a courtside table diving for a loose ball and ended up with beer spilled on his head. "He's from Wisconsin. He was right at home," Greg McDermott said. The comeback was one point short of Creighton's biggest at CenturyLink Center. The Bluejays rallied from 19 points down to beat Wichita State in January 2006.
QUOTE OF THE NIGHT
"It goes without saying that our crowd wouldn't let us quit. They wouldn't let us die." - Greg McDermott.
Oklahoma hosts Northwestern State on Sunday.
Creighton hosts North Carolina Central in Emerald Coast Classic on Sunday.