Stefan LeFors threw three touchdown passes and No. 12 Louisville rolled to a 55-28 victory over TCU on Wednesday.
LeFors, completing 75 percent of his passes coming into the game, went 13 for 21 for 275 yards as the Cardinals' top-ranked offense totaled 587 yards.
J.R. Russell and Broderick Clark caught two touchdown passes each for the Cardinals (7-1, 5-0 Conference USA), who beat the Horned Frogs for the first time in four meetings since 2001.
Louisville topped 50 points for the fourth time this season and went over 40 points for the ninth time in 21 games under second-year coach Bobby Petrino.
LeFors became the sixth Louisville quarterback to go over 5,000 career passing yards.
TCU (4-5, 2-4) allowed at least 40 points for the fifth time this season after giving up 40 points only five times in the previous six seasons.
Louisville's defense, meanwhile, held TCU to 308 yards after giving up 603 in a 56-49 win over Memphis last Thursday.
The Cardinals, leading the nation with 542 yards per game, raced to a 17-0 lead in the opening 6:53 -- before the Horned Frogs got their initial first down.
Louisville took the opening kickoff and marched down the field in six plays, averaging 11 yards per snap. Michael Bush finished the drive with a 12-yard scoring run.
After a TCU punt, LeFors scrambled twice to get the Cardinals across midfield again. He found Russell for a 32-yard touchdown pass with 10:06 left in the first quarter.
On the ensuing kickoff, Louisville's J.T. Haskins stripped the ball from Cory Rodgers and Louisville's Harry Douglas recovered at the TCU 38.
Art Carmody finished the Cardinals' scoring blitz with a 31-yard field goal.
At that point, the Horned Frogs had gained only seven yards on three plays and fumbled twice.
LeFors started 4-for-4, then misfired on five straight passes before consecutive completions to Tinch and Russell. Clark caught LeFors' next pass and outran a defender for a 42-yard touchdown, Louisville's longest scoring reception of the season.