SYRACUSE, N.Y. -- Ryan Nassib gave his hometown fans a memorable going away present.

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

Nassib directed an offense that gained 524 total yards. He went 15 of 23 and passed Donovan McNabb to move into second place on the Orange's passing yards list behind Marvin Graves.

He also set a Big East record by pushing his career completions to 738 and established an Orange single-season record for total offense (3,114).

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"We played mistake-free football, just tried to play our game and not do too much and had fun doing it," Nassib said. "Having success early on puts the pressure on the opposing team. It gets the momentum going and that's what happened today."

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.

Teddy 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.

"This was the worst game we ever played. They came out and got us," Louisville defensive back Hakeem Smith said. "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 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."

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.

Lemon roamed free through the Cardinals secondary all day, catching nine passes for 176 yards.

"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.