Gonzaga used a 14-4 run in the middle of the first half to take a 33-26 lead over San Francisco at intermission.
The Bulldogs took the lead for good, 14-12, on Elias Harris' transition layup with 14:53 left. The margin grew to five on Matt Bouldin's 6-foot bank shot and nine on Robert Sacre's dunk with 7:24 left.
San Francisco scored the next six points, but Gonzaga countered with eight of the last 12 points, capped by Steven Gray's bank shot with 46 ticks left.
Harris scored eight points, Sacre seven and Demetri Goodson six. Grant Gibbs (four points) gave GU its only bench points. Rashad Green led USF with nine points, but the Dons starting frontcourt of Tomas Bruha and leading scorer Dior Lowhorn each picked up three fouls.
The Bulldogs made 15 of 31 shots (48.4 percent), but just 1 of 7 free throws. The Dons hit 10 of 24 shots (41.7 percent).
More at the buzzer.