Iowa became the third No. 6 seed to fall in the first round of this year's NCAA Tournament as No. 11 seed Creighton led 34-31 at halftime and throughout the second half in advancing.
All-American Megan Gustafson did all she could for the Hawkeyes (24-8), producing her 28th double-double of the season with 29 points and 17 rebounds, but Creighton's guards provided the advantage.
The Bluejays (19-12) knocked down 9 of 24 3-point attempts, while Iowa was just 3 of 10 from distance and had 14 turnovers, nine in the first half.
Jaylyn Agnew led Creighton with 24 points on 8-for-14 shooting, including 4-for-6 from deep to go with five assists. Sydney Lamberty was just as good, knocking down 8 of 12 shots for 20 points while dishing six assists.
Creighton will play host No. 3 seed UCLA in the second round Monday.