This one looked painfully similar to last week's loss, with Renner overcoming a rough first half to throw four second-half touchdown passes and get North Carolina within five points.
The Tars Heels recovered a fumbled kickoff at Louisville's 23 with 4:15 remaining, and a chance to complete the comeback.
The Tar Heels got to the 3 but no closer, as Renner's intended pass for Erik Highsmith on fourth down was knocked away by Andrew Johnson in the end zone.
"I'll throw it to him again 100 times if we run that play," said Renner, who finished 26 of 41 for 363 yards and five touchdowns, tying a school record. "I've got confidence he's going to make the play but the defender made the play."
Said Highsmith, "I mean, I had it. I caught it. Coming down, he (Johnson) kind of took it out. He made a good play on it."
Now comes the matter of avoiding big holes to dig out of, which has happened two weeks in a row. Last week, it was a 21-14 halftime deficit at Wake Forest before North Carolina rallied to lead with 13 unanswered points before falling 28-27 after allowing a 93-yard TD drive.
This time, the Tar Heels trailed 36-7 at the half and 39-14 early in the fourth before Renner found his groove and the defense shut down the Cardinals (3-0). Mental mistakes and two first-half turnovers were to blame, and at times North Carolina just plain looked out of it.
"We came out playing football from another universe or something," tight end Eric Ebron said. "In the second, we got back down to Earth."
It was the Tar Heels second straight game without star tailback Giovani Bernard. Receiver Jheranie Boyd also sat out.
Cardinals coach Charlie Strong is off to the best start in his three seasons with Louisville.
"At the end of the day we still won the football game," Strong said. "We have us a good team and we just need to learn how to finish."
Louisville scored on its first six possessions thanks to three first-half touchdowns and 218 yards by Bridgewater. He finished 23 of 28 for 279.
Renner hit Romar Morris for a 50-yard touchdown on a screen pass with 4:23 remaining to make it 39-34.
North Carolina's Norkeithus Otis then forced Adrian Bushell to fumble the ensuing kickoff, and the Tar Heels recovered at the Cardinals' 10. But after moving to the 3, North Carolina was penalized for a false start. Two plays later Renner's fourth-down pass intended for Highsmith was batted away in the end zone by Johnson with 1:44 left.
"I thought second half we came back and competed our butts off," Renner said.
At the start, North Carolina was out of sync and dug its hole with two first-half turnovers that Louisville quickly converted.
"We came out playing football from another universe or something," Ebron said.
Right after Louisville marched 62 yards for its first touchdown and a 6-0 lead, Renner lofted a pass right at Louisville's Marcus Smith.
Bridgewater made it 12-0 on the next play, eluding the rush to find Charles Gaines wide open in the end zone on a post pattern.
After John Wallace's 22-yard field goal made it 15-0, Renner hit Morris for 15 yards, which would have left the Tar Heels with fourth down. But he fumbled after coming down with the ball, upheld on review, and was recovered by Adrian Bushell at North Carolina's 45.
Seven plays later Bridgewater hit Eli Rogers for a 15-yard score with the sophomore alone for the final 10. A rout was building at that point, and the Cardinals didn't let up.
Louisville went into sustained-drive mode, at least by its standards. The Cardinals went 84 yards but in just five plays, highlighted by Bridgewater's 36-yard crossing pass to Andrell Smith for first down at the Tar Heels' 44 and an 11-yarder to Scott Radcliffe.
Wright carried twice for the final 33 yards, capped by a 12-yard run. The next one went 10 plays and 69 yards, ending with Nick Heuser's 4-yard TD pass from Bridgewater.
"Last week we learned to come out and put our foot on the gas from the start," Bridgewater said. "This week, we learned we have to finish."
North Carolina got on the board with Renner's 44-yard scoring pass to Morris, cutting the lead to 29-7. The junior also hit Ebron for a 2-yard TD in the third quarter and Highsmith for a 9-yard score early in the fourth.