Cody Endres threw for 273 yards and a touchdown as UConn (4-2, 1-1) beat the Cardinals (2-4, 0-2) for the third consecutive season.
Marcus Easley had 108 receiving yards, including a 16-yard touchdown on a screen pass from Endres that helped UConn blow open a 14-13 game with 17 third-quarter points.
Louisville quarterback Adam Froman threw for 295 yards and two touchdowns, including a 4-yard scoring pass on the game's final play.
Louisville fumbled twice on third-quarter drives, once at the UConn 4-yard line with the Huskies leading 21-13. It was the Cardinals ninth loss in their last 10 games against Football Bowl Subdivision opponents.
Dixon gave UConn an early 7-0 lead when he juked past linebacker Preston Pace to score on a 16-yard run. That capped a 61-yard drive set up when Greg Lloyd Jr. tipped a pass, and Blidi Wreh-Wilson made the interception.
The Cardinals ate up over 9 minutes of the first half on a 19-play drive that tied the score 7-7 after a 1-yard plunge by Bilal Powell.
UConn needed just under 3 minutes to make it 14-7. Kashif Moore made a 66-yard catch and run to set up the score, breaking tackles down the UConn sideline to the 12-yard line. After a fourth-down conversion, Dixon took it into the end zone from a yard out.
UConn's final drive of the half ended when Endres through his first interception of the season, a pass that was tipped before being picked by Bobby Burns.
Powell ran for 87 yards on 29 carries for Louisville. The Cardinals' top rusher, Victor Anderson, didn't get a carry until the third quarter. He finished with 58 yards and a 2-yard touchdown run that capped a 74-yard drive in the fourth quarter.
Steve Kragthorpe is now 13-17 since taking over for Bobby Petrino three years ago.