Louisville vs SMU Prediction 11/22/2025 Today’s College Football Picks

The Louisville Cardinals and the SMU Mustangs meet Saturday in college football action from Gerald J Ford Stadium. Here’s a Louisville vs SMU prediction. We will look at this from a betting perspective and determine the best Louisville vs SMU pick. We will examine the recent form and player performances for both teams, as well as the recent betting trends and streaks pertaining to this matchup. As we conclude, we will tie it all together with a summary that produces a sensible pick for a favorable betting outcome in this game.

Louisville Cardinals Betting Preview

The Cards opened the season on a nice run, taking out Eastern Kentucky, James Madison, Bowling Green and Pitt before an overtime loss versus Virginia. Louisville beat Miami, Boston College and Virginia Tech after that before another overtime loss—this time to Cal. In that one Louisville posted a 10-6 second-half run to force the extra period but ended up losing 29-26 in the end. The Cardinals posted 351 total yards on offense with 16 first downs and a 6-of-17 success rate on third downs. The defense gave up 427 yards and 5.8 yards per play as well.

In their latest matchup last Friday versus Clemson, Louisville took another tight loss. The Cardinals were up 19-13 going into the final quarter then gave up an unanswered TD in a 20-19 finish. Miller Moss threw for 212 yards on 19-of-27 passing, and Keyjuan Brown led the rush with 15 carries for 135 yards. Chris Bell added five catches for 79 yards as the leading receiver.

SMU Mustangs Betting Preview

Over on the SMU side, they went 2-2 in their first four outings with wins over East Texas A&M and Missouri State among losses to Baylor and TCU. The Mustangs hit a 4-1 run after that, losing to Wake Forest with wins over Syracuse, Stanford, Clemson and Miami otherwise. In the 26-20 overtime win versus the Hurricanes, SMU hit a 13-10 second-half advantage to force the extra time. The Mustangs finished with 388 total yards but had only 23 rush yards and went 3-of-13 on third downs. SMU’s defense gave up 433 yards and 23 first downs in the win.

Matched up against Boston College in their most recent appearance on November 8, the Mustangs scored double-digit points in three of four quarters during a 45-13 road blowout. QB Kevin Jennings finished 16-of-32 for 326 yards, three scores and a pick. TJ Harden led the rush on 130 yards from 16 carries but Derrick McFall had three scores on five carries and 64 yards. Yamir Knight was tops in receiving with 162 yards and a TD on seven catches.

Louisville Cardinals @ SMU Mustangs Betting Trends: Week 13

SMU Mustangs Player Prop Facts

• Heading into Week 13, Kevin Jennings ranks 11th amongst FBS players for passing yards (2810) this season.

Louisville Cardinals Player Prop Facts

• Heading into Week 13, Isaac Brown leads the league for yards per carry (8.6) this season.

Matchup/League Facts

• SMU ranks 2nd among FBS teams for red zone percentage against this season (65.8).
• SMU ranks 4th among FBS teams for interceptions this season (16).
• Louisville ranks 13th among FBS teams for 4th down conversion percentage against this season (37.5).
• Louisville ranks 15th among FBS teams for 1st downs against this season (162).

Louisville vs SMU Prediction

I’ll lean toward SMU, but this should be a pretty good game overall. You could make a case either way. The Mustangs had no trouble with Boston College in their last outing, as the defense held the Eagles to just 2-of-15 on third downs alongside four takeaways. The offense managed a whopping 574 yards on the other side with 8-of-14 on third-down tries. It wasn’t all perfect though, as SMU committed 13 penalties for 155 yards. It’s been a nice couple of games for the Mustangs since their October 25 loss to Wake Forest 13-12.

As for Louisville, they went just 2-of-11 on third downs with 16 first downs and 10 team penalties in their latest loss to Clemson. The defense did a pretty good job overall, though. If the Cards can clean up their act I like a competitive matchup here. It’ll be a fun watch; Louisville has their work cut out for them if they want to avoid a three-game losing streak.

Andrew Jett's Pick: SMU Mustangs -3.5