Doug McDermott had 27 points and 11 rebounds, and Gregory Echenique scored 13 points to help Creighton hold on to beat Cincinnati 67-63 on Friday in the second round of the Midwest Regional.
Ethan Wragge added 12 for the Bluejays, who won their NCAA tournament opener for the second straight year.
McDermott, the two-time Missouri Valley Conference player of the year and 2012 All-American, made all 11 free throws to help the seventh-seeded Bluejays (28-7) move on to play Duke on Sunday.
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.