Teddy Bridgewater threw for 174 yards and scored two rushing touchdowns as Louisville beat Connecticut 34-20 on Saturday.
Victor Anderson added 72 yards rushing for Louisville (6-5, 4-2 Big East), which kept its title hopes alive in a tightly packed conference. Bridgewater completed 14 of 22 passes with an interception.
UConn (4-6, 2-3), which last year won its final five regular season games to win the league championship and earn a trip to the Fiesta Bowl, is now mathematically out of the race.
The Cardinals had lost three of their last four games to UConn though they did handle the Huskies easily last season, winning 26-0 in Louisville.
Johnny McEntee was 18 of 43 passing for 253 yards for UConn. Kashif Moore caught six passes for 110 yards and a TD and also scored a rushing touchdown.
Lyle McCombs rushed for 33 yards - well under his 109-yard per-game average - but did become the second UConn freshman to pass the 1,000-yard mark.
In a game dominated by defense for long stretches, the Cardinals pulled away when their offense finally hit its stride.
Bridgewater scored on a 5-yard run late in the third quarter to put his team ahead 21-10. His option-keeper capped a 95-yard drive that was jumpstarted by a running-into-the-kicker penalty on UConn's Kendall Reyes, and kept alive by a 39-yard pass to Andrell Smith down the sideline.
The Cardinals appeared to put the game away early in the fourth quarter on Bridgewater's second score. The touchdown, which made it 28-10, was preceded by Josh Bellamy's 35-yard, juggling catch.
UConn closed the gap with 8:34 to play in the game when McEntee hit Moore with a 30-yard touchdown pass.
A field goal by the Huskies with 13 seconds left pulled them within 28-20, and the successful onside kick that ensued gave them a slim chance of sending the game to overtime.
Although the game's final play was a completed McEntee pass, it was followed by a series of laterals and resulted only in another Louisville score. Malcolm Mitchell picked off the final pitch and returned it 36 yards for a touchdown.