The Golden Bears (20-7, 12-4 Pac-12 Conference) reached the 20-win mark for the third straight season under coach Lindsay Gottlieb, who is now 77-21 since coming to Berkeley in 2011.
Cal opened a 10-point lead in the first half before the Trojans (16-12, 9-7) closed the half on an 8-2 run.
But Reshanda Gray scored the first eight points of the second half to put the Bears back up by 12 and Cal opened its biggest lead at 49-32 on Mikayla Lyles’ 3-pointer with 16 minutes to go.
USC would get no closer than eight points the rest of the way.
Gray paced the Golden Bears with 22 points and 11 rebounds and Afure Jemerigbe notched 16 points and seven assists.
Cassie Harberts scored 18 points and had four assists for the Trojans. Kiki Alofaituli and Ariya Crook each had 10 points, with Crook also dishing four assists. Alexyz Vaioletama had seven rebounds and three steals.
The Golden Bears had a 38-30 edge on the boards and had 15 turnovers, while the Trojans gave the ball away 13 times.
Cal returns home to close out the regular season, starting its final two-game homestand Thursday night against Washington State at 6 p.m.