Louisville's perfect start appeared to be over before Teddy Bridgewater came up with one more big play.
Bridgewater threw an 11-yard touchdown pass to Eli Rogers with 1:35 left, and the 16th-ranked Cardinals edged South Florida 27-25 on Saturday for their best beginning to season since 2006.
Louisville (7-0, 2-0 Big East) rallied after yielding 15 straight points to South Florida and a season-high 197 yards rushing.
B.J. Daniels threw three TD passes in the second half, the last one putting South Florida ahead 25-21 with 3:09 left. The Bulls had one last chance for the win, but Adrian Bushell intercepted Daniels' last-gasp throw as time ran out, well short of the end zone.
South Florida (2-5, 0-3) has dropped five straight games. It has just one win in its last 12 conference games dating to last season.
Louisville finished with four sacks and a big goal-line stand late in the third quarter. Bridgewater was 21 of 25 for 256 yards and two TDs, and the sophomore quarterback also led the Cardinals with 74 yards rushing on 10 carries.
South Florida outgained Louisville 386-384, and the Bulls grabbed the lead by scoring 15 straight points after Louisville stopped them during a goal-line stand in the third quarter when South Florida thought it had scored not once but twice.
First, Lindsey Lamar appeared to score on first-and-goal on a 4-yard run. But officials ruled Lamar down at the 1. Daniels tried to sneak in and was stopped. Demetrius Murray couldn't score on third down. Then Daniels pushed up through the left side on fourth down and into the end zone.
But officials flagged Louisville defensive end Marcus Smith for jumping offsides, forcing South Florida to line up one more time. Daniels kept the ball and was stopped yet again, sparking a big celebration by Louisville.
The Bulls closed to 21-18 after Daniels directed an 86-yard, 14-play drive, including a fourth-down conversion. He finished it off with a 13-yard TD pass to Sean Price with 8:02 left. When Louisville was flagged for being offside on the extra point, the Bulls gave the ball to Murray for the 2-point conversion.
Daniels then found Andre Davis for a 12-yard score to make it 25-21. The drive featured a defensive pass interference call on Bushell where the ball appeared uncatchable out of bounds.
Bridgewater, who completed his first 11 passes of the game, responded by leading the Cardinals on a 75-yard drive. He set up the winning TD pass by scrambling 11 yards, and officials flagged Bulls cornerback Kayvon Webster for a late hit as the QB went out of bounds. A play later, Bridgewater found Rodgers at the back of the end zone.
DeDe Lattimore blocked John Wallace's extra point, giving the Bulls a chance to win with only a field goal. But the Cardinals got their fourth sack of Daniels on The Opening play of the resulting drive. With no timeouts, the Bulls' last gasp came on third-and-10 when Bushell grabbed Daniels' last pass.