Up ahead, No. 3 seed Duke on Sunday.
"Since last season, we wanted to get back to this game," said McDermott, the two-time Missouri Valley Conference player of the year.
The Bluejays (28-7) moved on to the third round for the second straight season. They were eliminated by North Carolina at that point last year. Now, the ACC stands in their way again.
"We've been shooting for this game for a year, wanting to get back to have an opportunity to play to get into the Sweet 16," Creighton coach Greg McDermott said.
Gregory Echenique scored 13 points and Ethan Wragge added 12 for the Bluejays, who overcame 30 percent shooting in the second half.
Sean Kilpatrick's driving layup after Cincinnati had the arrow on a jump ball cut it to 64-63 with 17 seconds left.
Austin Chatman sank two free throws for Creighton. Kilpatrick's attempt at a tying 3 rimmed out, and the Bearcats were whistled for traveling after grabbing the rebound.
Chatman then hit one of two from the line to clinch it.