Louisville Cardinals vs SMU Mustangs Prediction, 11/22/2025 College Football Picks, Best Bets & Odds

Game: Louisville Cardinals vs SMU Mustangs

Date: Saturday, November 22, 2025

Location: Gerald J. Ford Stadium in Dallas, TX

TV: ESPN2

Odds/Point Spread: Mustangs (-3.0)

Total/Over-Under: 52.5

The SMU Mustangs (7-3) will try to defeat the Louisville Cardinals (7-3) at Gerald J. Ford Stadium on Saturday, November 22, 2025. SMU opens this matchup as 3.0-point favorites from Vegas oddsmakers. The total is set at 52.5.

The Louisville Cardinals head into this matchup 7-3 this year. The last time they stepped onto the field, the Cardinals stepped onto the field against the Clemson Tigers and went home with a loss by a final score of 20-19. The Louisville Cardinals ran the rock 30 times and compiled 171 yds, which is an average of 5.7 yds per attempt. On the day, they had 59 plays which gave them a total of 385 yds. Louisville relinquished 31 pass completions on 49 attempts for a total of 350 yds, and a completion rate of 63.3%. In the running game, the Cardinals conceded 77 yards on 25 tries, which is an average of 3.1 yds per run allowed.

The Cardinals have tallied 3,998 total yards for the season. In terms of scoring, Louisville has compiled 13 touchdowns via the pass and 21 touchdowns via the ground. They have turned the football over 15 times. Louisville has accumulated 197 first downs as an offense, and they have been called for 69 penalties for 652 yds. As a team they maintain an average of 156.5 yards in the run game which has them sitting 71st in D-1. When talking about putting the ball in the endzone, the Louisville Cardinals are sitting at 31.5 points per game.

The Cardinals are ranked 39th in the nation concerning the opposition scoring, allowing 21.5 points per contest. The opposition is running for an average of 3.4 yards per running attempt and 109.9 rushing yards per game on the campaign. In total, they have allowed 1,099 yards via the ground game in 10 contests. When talking about yards via the pass, the Cardinals have given up 1,880 yards which puts them in 26th in college football. They have yielded 188.0 yards per contest via the pass as well as conceding a completion percentage of 57.4%. During this campaign, they have allowed 297.9 yards/game which puts them 16th in Division 1. They have allowed 11 touchdowns by air and 10 touchdowns running the ball.

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The Mustangs head into this game 7-3 for this season. When they last stepped on the field, the Mustangs got the win with a final of 45-13 against the Boston College Eagles. SMU gave up 40 run attempts for 98 yds (2.5 yards per carry). The Mustangs pass defense allowed a completion rate of 64.4%, relinquishing 284 yards on 29 for 45 passing. The Mustangs finished the game with a total of 574 yds while running 66 plays (8.7 yards per play). SMU rushed the ball for 7.2 yds per carry, finishing with a total of 222 yds on 31 carries.

The SMU Mustangs have an average of 406.6 yards per contest, ranking them 54th in the country. The SMU offense has accrued 712 penalty yards on 69 infractions, which has them sitting 37th in college football in terms of helping out the opposition. They are averaging 122.1 rushing yards per game and have run for 1,221 yards in total. They have thrown 9 picks while letting opponents recover 6 fumbles and they have been able to tally 200 1st downs. In relation to the points being put on the board, the Mustangs currently rank 40th in Division 1 by scoring 32.2 points per game. For the season to this point, the Mustangs have thrown for 2,845 yards via the pass as well as holding an average of 284.5 passing yards per contest, giving them a rank of 18th in the country.

SMU has allowed a total of 1,021 rushing yards (102.1 yards per game) in addition to 4 touchdowns on the ground for the season. They have surrendered 19 touchdowns through the air in addition to 298.6 yards/outing, ranking them 135th in D-1. In total, they have surrendered 204 total points. They have compiled 10 fumbles recovered and 16 interceptions for the season. The Mustangs defense has been on the field for 773 plays, which has them ranked 134th in the country. The Mustangs are relinquishing 20.4 PPG, which puts them 31st in college football.

Who will win tonight's Cardinals/Mustangs college football game against the spread?

Guy's Pick: Take the Mustangs -3.0

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