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.
McDermott has said he'll wait until after the season to decide if he'll return for his senior year. He's projected as a late first- or early second-round pick and could probably boost his stock with a strong season against tougher teams in a new-look Big East.
The Bluejays could never put away the 10th-seeded Bearcats (22-12) in their camouflage-patterned shorts.
Echenique snapped a tie with a layup and McDermott hit two from the free-throw line to help the Bluejays keep the lead over the final 3 minutes.
For all their offensive woes, the Bearcats stayed close and never trailed by more than eight in the second half. Cashmere Wright hit a 3 -- Cincinnati's fourth on 15 attempts -- to slice it to 52-49.
McDermott had a rare miss inside and showed some visible frustration, clapping his hands trying to rally the Bluejays. Kilpatrick hit two free throws to pull the Bearcats within two. He sank consecutive jumpers to tie the game at 54-54 with 3:33 left.
That was pretty much all the Bearcats had left, and they're heading home a year after reaching the round of 16. Except for a 5-minute spurt midway through the second half to help them tie the game, they couldn't buy a bucket.
McDermott was double-teamed in the corner and swung his left elbow into Shaquille Thomas' face to break free with 53 seconds left. McDermott was whistled for a flagrant foul and Thomas went to the line but missed both free throws.
Wright, though, buried a 3 on the ensuing possession to make it 60-57. The Bearcats could just never take the lead.
Kilpatrick scored 19 points, and Wright had 15.
Creighton, Butler and Xavier are set to shed the mid-major label and join Big East holdovers Georgetown, St. John's, Villanova, Marquette, Providence, Seton Hall and DePaul next season. Cincinnati is staying behind in the football-based, soon-to-be-former Big East.
The Bearcats struggled to score all season and had little production after Wright hit two quick 3s to open the game. Each team made 12 shots in the half. The difference was in efficiency. The Bearcats were 12 of 33 while Creighton was 12 of 19. The Bearcats even forced 10 turnovers and it still wasn't enough.
McDermott had a quiet half until the final minutes. He hit his first 3-pointer, then got the ball in the low post and twirled around for a layup. He sank the free throw to complete the three-point play to send the Bluejays into halftime with a 32-27 lead.
Led by McDermott's flawless effort from the line, the Bluejays made 22 of 25 free throws. The Bearcats made only 4 of 9, and that doomed them down the stretch.
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