The Gamecocks (15-4, 4-2 Southeastern Conference) saw a 13-point lead disappear with 11 minutes left. Then Downey, who had just six points at that stage, got going.
He had two foul shots to put South Carolina ahead for good, 50-49, then followed with a spinning basket in the lane to keep momentum. By the time Downey drove past Jermaine Beal for a layup, the Gamecocks were ahead 70-56 with 4:51 left.
Vanderbilt (12-8, 1-5) lost its fourth in a row and fifth in the past six games.
South Carolina's latest win surpassed its victory total of the past two seasons.
Jeffrey Taylor had 23 points to lead Vanderbilt. However, he was among three Commodores who fouled out.