With the win, Saint Mary's improves to 9-4, 1-0 WCC, while San Francisco drops to 7-7, 0-1 WCC.
Danielle Mauldin led the way for SMC with 16 points and 14 rebounds, while Kate Gaze added 14 points and Jackie Nared with 12 points. Hayley Hendricksen grabbed a career-high nine rebounds off the bench in 14 minutes of action.
The Gaels used a 9-0 run in the first half, capped by a Gaze three-pointer to open up a 22-11 lead.
Saint Mary's got a strong contribution from the bench in the first half, finishing the final 2:30 with one starter on the court and extending the lead. Saint Mary's led 34-24 at the break.
The Dons pulled within four points in the second half at 40-36, with 15:16 left. Saint Mary's quickly responded with a n 8-1 run to pull ahead 48-37 with 9:34 remaining. USF would pull no closer than nine points the rest of the way as SMC cruised in the final minutes to the 68-48 win.
Saint Mary's outrebounded USF 45-34 and held USF to just a 28.8 percentage from the field. Saint Mary's was also solid from the free-throw line, connecting on 82.5 percent going 29-for-35 from the line.
Saint Mary's is back in action on Saturday when it travels to Loyola Marymount. Tip is set for 2:00 p.m. in Gersten Pavilion.