Behind a career-high 35 points from guard Andrea Smith, the visiting Bulls raced to an early first half lead and never surrendered.
Louisville (21-6, 9-4)used a 9-0 run to trim the USF lead to 24-22 at the half, but that was as close as they could get for the rest of the game.
In front of 8,201 at the KFC Yum! Center, the Cardinals shot a season low 30% from the field, while the Bulls shot 47%, including a blistering 50% (8-16) from beyond the three-point arc.
Schoni Schimmel led the Cardinals with 16 points. Sara Hammond recorded her second consecutive double-double with 10 points and 12 rebounds.
Louisville returns to action on Sunday afternoon at Villanova, with a 2:00 p.m. tip-off.