Central Florida (10-1, 7-0 American Athletic Conference) clinched a share of the league crown. A win over SMU next week will give the Knights the undisputed title.
Bortles completed 17-of-26 passes for 219 yards with two touchdowns. He was intercepted twice, however, and Central Florida committed five turnovers overall.
That allowed South Florida to stay in the game and the Bulls took the lead when Marcus Shaw scored on a 1-yard run 43 seconds deep into the fourth quarter.
After the Knights regained the advantage, South Florida quarterback Mike White was intercepted to cost the Bulls a chance at victory. South Florida (2-9, 2-5) lost its fifth in a row.