Ragone scored on a 27-yard run and a one-yard plunge as Louisville (8-1, 4-0 C-USA) took a 14-7 lead in the first quarter. Henry Miller added a 41-yard touchdown run for a 14-point lead at the end of the first.
Ragone threw first touchdown pass of the game, an 11-yarder to Tony Stallings, before a 45-yard field goal by Nathan Smith with 44 seconds left gave the Cardinals a 31-7 halftime edge.
Chip Mattingly caught a one-yard touchdown pass from Ragone and J.R. Russell hauled in a 21-yard touchdown reception in the third quarter. Miller added a nine-yard scoring run in the fourth.
Miller carried nine times for 121 yards while T.J. Patterson also topped the century mark with 101 yards rushing. Even Ragone got into the attack, outrushing the entire Tulane team, 56-19.
Louisville, which moved into a tie for first place with idle East Carolina, outgained the Green Wave, 573 yards to 239. Ragone completed 19 of 30 passes for 232 yards.
Tulane (2-8, 1-5) got its lone touchdown on a 43-yard pass from Patrick Ramsey to Tristan Smith that opened the scoring. Ramsey was 15 of 30 for 172 yards and two interceptions.