The No. 16-seed Bluejays concluded their season at 27-9 after advancing past the second round of the NCAA Tournament for the first time in program history.
"From last spring, preparing for this season, our goal has been to make it to the Sweet 16," senior setter Maggie Baumert said. "I really felt like this entire season we took game-by-game, step-by-step, point-by-point, and we made our goal."
Baumert had 37 assists on Friday night.
Freshman outside hitter Jaali Winters led the Jays with 12 kills.
Creighton jumped out to an early lead in set No. 1 before USC took its first lead 11-10.