Louisville's run at a perfect season can came to an ugly and decisive end.

Syracuse's Ryan Nassib threw for 246 yards and three touchdowns in his final home game, and moved into second on the school's career passing list as the Orange handed No. 11 Louisville its first loss of the season in a 45-26 victory on Saturday.

"I am very embarrassed today for our program" Louisville coach Charlie Strong said. "We didn't play well — the preparation and the execution weren't there. We didn't play well in all three phases. We have a lot to learn from this game. Now we have to go back. We have two more games and have to see where this football team is. This was a good experience for us - to come into a hostile environment and see how we could play and we just didn't play well today."

Defensive back Hakeem Smith and quarterback Teddy Bridgewater were all too quick to agree.

"This was the worst game we ever played," Smith said. "They came out and got us. There's not a lot of talking (in the locker room) right now. We just have to push on. We're going to bounce back."

The Orange (5-5, 4-2 Big East) blew the game open with three touchdowns in the second quarter and Louisville (9-1, 4-1) allowed more points than it had in any game this season. Syracuse is a win away from bowl eligibility with road games against Missouri and Temple left.

Jerome Smith ran for 144 yards for Syracuse and Prince-Tyson Gulley added 98 yards rushing and two touchdowns.

Bridgewater completed 36-of-49 passes for 426 and three touchdowns for Louisville, who fell into second place behind Rutgers in the Big East race.

"They played the deep ball, but they still had guys make plays underneath," said Bridgewater. "It was nothing new, nothing we hadn't seen all week. It was just a lack of execution.

The Cardinals, who are off next Saturday, still play Connecticut and Rutgers.

"They played well today. You have to give them credit for playing so hard," Cardinals linebacker Preston Brown said of the Orange. "It's disappointing having all this (a perfect season) down the drain. But we can still win the Big East."

Alec Lemon had nine receptions for 176 yards and two TDs for Syracuse.

The Orange racked up 339 yards of total offense in the first half while breezing to a 31-13 lead at half. Smith piled up 72 yards of those yards on the ground, and Nassib completed 10 of 17 for 185 yards and two touchdowns to Alec Lemon.

Gulley broke around the right side for a 55-yard touchdown romp to put the Orange up by 21 with 2:13 left in the half. He also had an 8-yard touchdown run in the first quarter.

Louisville's John Wallace nailed a 35-yard field goal with 9 seconds left to set the halftime score.

"We knew coming in Louisville plays man-to-man. It came down to who wanted it more. We harped on it a lot. We need to win every play," Lemon said.

The Orange were content to trade scores with the Cardinals in the third. Smith rumbled for a 35-yard touchdown to make it 38-13 with 9:47 left in the third, and Louisville responded with a 44-yard touchdown pass from Bridgewater to Eli Rogers with 1:49 remaining to pull within 38-19.

In the fourth, Nassib hit Lewellyn Coker for a 3-yard scoring pass with 11:14 remaining, and Bridgewater countered with an 8-yard touchdown pass to DeVante Parker with 8:53 left.