The nation's top-rated passer completed 19 of 27 for 247 yards before leaving the game late in the third quarter. LeFors, a senior, was not recruited by a single Louisiana college but has become the triggerman for one of the most prolific offenses in the country at Louisville.
The Cardinals (10-1, 8-0 Conference USA), ranked first nationally in scoring, were averaging nearly 50 points a game. They reached the 55-point mark for the fifth straight game.
Louisville's lowest scoring game was a 28-0 victory over Kentucky in the season opener. Since then, the Cardinals have scored no fewer than 34 points, and more than 40 points seven times.
Louisville had already clinched the conference regular-season title and a spot in the Liberty Bowl. Tulane (5-6, 3-4) had won three straight, and was hoping for an upset and a shot at a bowl game.
The regular-season finale for both teams was originally scheduled for Sept. 18, but was postponed when Hurricane Ivan threatened the New Orleans area.
Louisville had 522 yards in total offense to 165 for Tulane. The Cardinals had 26 first downs to nine for the Green Wave.
Tulane's defense managed to hold the Cardinals to field goals on two of their three scoring drives in the first quarter.
Louisville capped its opening possession with a 30-yard field goal, going up 3-0. On their second possession the Cardinals drove 67 yards with Eric Shelton rushing the final yard to make it 10-0.
Jon Russell blocked a punt that was recovered by Lou Harris, setting Louisville up on the Green Wave 12. The Cardinals settled for a field goal again, however, a 33-yarder that made it 13-0 at the end of the first quarter.
Tulane opened the second quarter with a goal-line stand, stopping Louisville four times from inside the 3-yard line. It was moot when Tulane quarterback Richard Irvin fumbled the snap in the end zone. Montavious Stanley dove under the Green Wave center and recovered the football for a Louisville touchdown that made it 20-0.
Louisville closed out the first half with a 3-yard touchdown rush by LeFors to make it 27-0.
In the fourth quarter Shelton rushed for a 5-yard score and Kolby Smith ran for a 7-yard TD.
Tulane prevented the shutout with a 3-yard touchdown pass from Irvin to Roydell Williams with 2:12 left in the game.