Jasmine Lister had 11 points and six assists for Vanderbilt (10-3).
USC led 33-31 at halftime.
In the second half, Vanderbilt made a run, outscoring USC 14-2 to take a 50-39 lead at the 14:36 mark. The Commodores did not relinquish their lead.
The Commodores shot 47 percent from the field for the game, while the Trojans shot 39 percent.
Cassie Harberts led USC with 22 points and seven rebounds. Ariya Crook had 12 points.
The Trojans (3-8) have lost six consecutive games.