Daniel Ochefu added 12 points for Villanova (11-4, 2-0 Big East), which has won seven in a row.
South Florida (9-5, 0-2) got 12 points from Victor Rudd. The Bulls had won the four previous games between the programs, including all three last season.
Ryan Arcidiacono, the Big East Rookie of the Week, gave Villanova a 46-32 lead on his first basket of the game, a 3-pointer, midway through the second half. The freshman, averaging 13 points, finished with five points.
Pinkston's layup made it 48-32 one minute after Arcidiacono's basket.
Rudd connected on a 3 to cut the South Florida deficit to 49-41 with 7 minutes remaining. Villanova quickly responded on baskets by Yarou and Ochefu to make it 53-41
After trailing by 18 early in the second half, South Florida got within 42-30 on a pair of free throws by Rudd with 13 minutes to play. It was the first bucket of the game for Rudd, who entered averaging a team-best 11.5 points.
South Florida point guard Anthony Collins had 11 points.
Ochefu had 10 points as Villanova grabbed a 34-20 halftime lead.
The Wildcats took a 29-14 advantage 2 minutes before intermission on a long-range jumper by Achraf Yacoubou. Two free throws by Yarou extended the Villanova lead to 34-17.
Darrun Hilliard made a 3-pointer and Pinkston had a put-back basket to put Villanova up 13-6 with 13 minutes left in the opening half.