Louisville vs. Clemson Prediction, Odds, Picks - November 14, 2025

Updated Nov. 14, 2025 3:05 p.m. ET

Data Skrive

Two of the nation's top run defenses meet when the No. 19 Louisville Cardinals (7-2) bring college football's 22nd-ranked rushing defense into a matchup with the Clemson Tigers (4-5), who have the No. 20 rushing defense, on Friday, November 14, 2025. The Cardinals are only 2.5-point favorites. The over/under is set at 50.5 for the contest.

Last time around, the Cardinals fell to the California Golden Bears, with 29-26 being the final score. The Tigers beat the Florida State Seminoles, 24-10, in their most recent contest.

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Louisville vs. Clemson Game Information & Odds

When: Friday, November 14, 2025 at 7:30 p.m. ET
Location: L&N Federal Credit Union Stadium in Louisville, Kentucky
TV: ESPN
Live Box Score on FOX Sports

Louisville vs Clemson Betting Information updated as of November 14, 2025, 2:45 p.m. ET.
Favorite	Spread (Odds)	Favorite Moneyline	Underdog Moneyline	Total	Over Moneyline	Under Moneyline
Louisville	-2.5 (-110)	-130	+110	50.5	-112	-108

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Louisville vs. Clemson Prediction

Pick ATS: Louisville (-2.5)
Pick OU: Over (50.5)
Prediction: Louisville 31, Clemson 20

Predictions are made by the Data Skrive betting model.

Learn more about the Louisville Cardinals vs. the Clemson Tigers game on FOX Sports!

Louisville vs. Clemson Betting Insights

Per the spread and over/under, the implied score for the matchup is Cardinals 26, Tigers 24.
The Cardinals have a 56.5% chance to claim victory in this meeting per the moneyline's implied probability. The Tigers hold a 47.6% implied probability.
Louisville is 3-6-0 ATS this season.
Clemson has put together a 3-6-0 ATS record so far this season.

Louisville vs. Clemson: Head-to-Head

Clemson holds a 2-1 record against Louisville in their last three matchups.
In those games against Louisville, the Tigers have covered two times while outpacing the total on one occasion.
In their last three head-to-head matchups, Clemson has scored 82 points versus Louisville, while surrendering only 73 points.

Louisville vs. Clemson: 2025 Stats Comparison

	Louisville	Clemson
Off. Points per Game (Rank)	32.9 (43)	27.9 (73)
Def. Points per Game (Rank)	21.7 (33)	22.4 (44)
Turnovers Allowed (Rank)	14 (98)	13 (85)
Turnovers Forced (Rank)	16 (21)	10 (86)

Louisville 2025 Key Players

Name	Position	Stats
Miller Moss	QB	2,132 YDS (63.8%) / 11 TD / 7 INT -73 RUSH YDS / 7 RUSH TD / -8.1 RUSH YPG
Chris Bell	WR	62 REC / 792 YDS / 6 TD / 88 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
Keyjuan Brown	RB	457 YDS / 6 TD / 57.1 YPG / 6.9 YPC 9 REC / 104 REC YDS / 0 REC TD / 14.9 REC YPG
TJ Quinn	LB	57 TKL / 3 TFL / 1 SACK / 2 INT
Antonio Watts	LB	30 TKL / 4 TFL / 2.5 SACK / 3 INT
Wesley Bailey	DL	32 TKL / 4 TFL / 5 SACK
D'Angelo Hutchinson	DB	54 TKL / 2 TFL / 1 INT / 1 PD

Clemson 2025 Key Players

Name	Position	Stats
Cade Klubnik	QB	2,136 YDS (67.9%) / 14 TD / 5 INT 117 RUSH YDS / 3 RUSH TD / 14.6 RUSH YPG
Adam Randall	RB	570 YDS / 6 TD / 63.3 YPG / 4.9 YPC 26 REC / 212 REC YDS / 3 REC TD / 26.5 REC YPG
Bryant Wesco Jr.	WR	31 REC / 537 YDS / 6 TD / 76.7 YPG
T.J. Moore	WR	31 REC / 536 YDS / 4 TD / 59.6 YPG
Sammy Brown	LB	61 TKL / 6 TFL / 3 SACK
Avieon Terrell	DB	36 TKL / 3 TFL / 3 SACK
Wade Woodaz	LB	50 TKL / 4 TFL / 0.5 SACK
Will Heldt	DL	29 TKL / 8 TFL / 4 SACK