Louisville Cardinals vs SMU Mustangs Prediction - 11/22/2025
Updated November 21, 2025
Updated November 21, 2025
The Louisville Cardinals (7–3) head into a critical ACC showdown with the SMU Mustangs (7–3) on Saturday afternoon. SMU is jockeying for position in the ACC title race as one of four teams with just one loss in conference play. They will try to stay at one conference loss with a win at home over a desperate Louisville team. I have broken down this matchup from all angles. You can find my SMU vs Louisville prediction right here.
SMU has everything to play for in this game. With a 5–1 ACC record, a win keeps their shot at the conference title game alive. Louisville has dropped two straight games and is reeling from a 20-19 loss to Clemson where a pair of missed field goals proved costly. Louisville is out of ACC title contention because of those losses, but will still try to improve their bowl assignment by winning more games.
Injuries are biting Louisville hard late in the season. Starting quarterback Miller Moss is listed as questionable, while lead running back Keyjuan Brown is officially out for this contest. That could force Louisville into a more limited offensive approach, and they could struggle to run the ball more than usual.
SMU has won two games in a row. They followed up their overtime upset of Miami with a 45–13 win over Boston College. SMU piled up 574 yards of offense in that game against the Eagles. The Mustangs know that a win keeps their ACC title goal in reach. But they can't afford to take this game for granted despite being a home favorite.
Louisville’s Miller Moss has thrown for 2,344 yards this season with 11 touchdowns and 7 interceptions. He’s a veteran presence, but his season has been up and down and any injury issues for Moss could hamper Louisville’s chances of winning this game.
SMU’s signal-caller is Kevin Jennings. He’s thrown for over 2,800 yards with 21 touchdowns and 9 interceptions. He showed big-time confidence in a recent win over Syracuse, tossing four touchdowns on 29 of 35 passing.
Score Projection: SMU 28 – Louisville 23
Win Probability: SMU 60%, Louisville 40%
Both teams still have plenty to play for late in the regular season. But SMU has more to play for, as they still have a shot at a conference title this season. More importantly, SMU has an offense that is a lot more trustworthy thanks to the health questions surrounding Moss. I'll lay the points with SMU at home in this game in the ACC.
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