SMU vs. Louisville Prediction, Odds, Picks - November 22, 2025

Updated Nov. 22, 2025 9:04 a.m. ET

Data Skrive

Two of the nation's top rushing defenses meet when the SMU Mustangs (7-3) take college football's 14th-ranked rushing defense into a matchup with the Louisville Cardinals (7-3), who have the No. 23 rushing defense, on Saturday, November 22, 2025. The Mustangs are 3.5-point favorites. The over/under is 49.5 for this matchup.

In their last action, the Mustangs won against the Boston College Eagles, 45-13. In their last contest, the Cardinals lost versus the Clemson Tigers, 20-19.

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SMU vs. Louisville Game Information & Odds

When: Saturday, November 22, 2025 at 12 p.m. ET
Location: Gerald J. Ford Stadium in University Park, Texas
TV: ESPN2
Live Box Score on FOX Sports

SMU vs Louisville Betting Information updated as of November 22, 2025, 8:45 a.m. ET.
Favorite	Spread (Odds)	Favorite Moneyline	Underdog Moneyline	Total	Over Moneyline	Under Moneyline
SMU	-3.5 (-118)	-181	+151	49.5	-111	-109

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SMU vs. Louisville Prediction

Pick ATS: Pick Em
Pick OU: Over (49.5)
Prediction: SMU 28, Louisville 24

Predictions are made by the Data Skrive betting model.

Learn more about the SMU Mustangs vs. the Louisville Cardinals game on FOX Sports!

SMU vs. Louisville Betting Insights

Based on the spread and over/under, the implied score for the game is Mustangs 26, Cardinals 23.
The Mustangs have a 64.4% chance to claim victory in this meeting per the moneyline's implied probability. The Cardinals hold a 39.8% implied probability.
SMU has covered four times in nine chances against the spread this season.
Louisville has won three games against the spread this season, failing to cover seven times.

SMU vs. Louisville: 2025 Stats Comparison

	SMU	Louisville
Off. Points per Game (Rank)	32.2 (40)	31.5 (46)
Def. Points per Game (Rank)	20.4 (30)	21.5 (36)
Turnovers Allowed (Rank)	15 (92)	15 (92)
Turnovers Forced (Rank)	26 (1)	17 (25)

SMU 2025 Key Players

Name	Position	Stats
Kevin Jennings	QB	2,810 YDS (64.8%) / 21 TD / 9 INT 26 RUSH YDS / 2 RUSH TD / 2.6 RUSH YPG
Tomarion Harden	RB	612 YDS / 6 TD / 61.2 YPG / 4.6 YPC 14 REC / 73 REC YDS / 0 REC TD / 12.2 REC YPG
Jordan Hudson	WR	42 REC / 595 YDS / 4 TD / 74.4 YPG
Romello Brinson	WR	40 REC / 582 YDS / 3 TD / 58.2 YPG
Ahmaad Moses	DB	60 TKL / 4 TFL / 1 SACK / 5 INT
Isaiah Smith	DL	34 TKL / 10 TFL / 8 SACK
Isaiah Nwokobia	DB	63 TKL / 0 TFL / 2 INT / 2 PD
Cam Robertson	DL	31 TKL / 5 TFL / 5 SACK

Louisville 2025 Key Players

Name	Position	Stats
Miller Moss	QB	2,344 YDS (64.3%) / 11 TD / 7 INT -76 RUSH YDS / 8 RUSH TD / -7.6 RUSH YPG
Chris Bell	WR	67 REC / 871 YDS / 6 TD / 87.1 YPG
Keyjuan Brown	RB	592 YDS / 6 TD / 65.8 YPG / 7.3 YPC 11 REC / 118 REC YDS / 0 REC TD / 14.8 REC YPG
Isaac Brown	RB	782 YDS / 5 TD / 97.8 YPG / 8.6 YPC 11 REC / 42 REC YDS / 0 REC TD / 10.5 REC YPG
Antonio Watts	LB	37 TKL / 5 TFL / 2.5 SACK / 3 INT
TJ Quinn	LB	62 TKL / 3 TFL / 1 SACK / 2 INT
Clev Lubin	DL	36 TKL / 3 TFL / 4.5 SACK
Wesley Bailey	DL	34 TKL / 4 TFL / 5 SACK