Clemson vs. Louisville, Preview, Odds, Picks and Prediction for Friday, November 14, 2025
Use Code WWWC On Friday night, the Louisville Cardinals will host the Clemson Tigers for a Week 12 NCAAF game at L&N Federal Credit Union Stadium. The Atlantic Coast Conference matchup is scheduled for 7:30 p.m. ET.
The Cards are three-point spread favorites, and the total is 50 points scored.
This Clemson vs. Louisville prediction highlights a Tigers team that has been a major disappointment and a Cardinals squad that's coming off an upset loss at Cal. Clemson leads the all-time series 8-1, but the Cardinals won last year's matchup 33-21 in South Carolina.
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Clemson QB Klubnik has improved his play recently
Clemson (4-5 SU, 3-6 ATS, and 4-5 O/U) beat Florida State 21-10 last weekend, snapping a two-game losing streak. The Tigers (3-4 in ACC play) were picked to win the ACC and were a national title favorite, but will need to win two of their next three games to earn a bowl invitation. In short, it's been a major disappointment for a team that was considered a national championship contender heading into the season.
Clemson took an early 18-0 lead and never looked back last week, forcing two turnovers and dominating the time of possession. The Tigers entered the matchup 1-4 at home this season and had lost their previous six games against Power 4 programs. FSU outgained Clemson, but was a combined 6-for-18 on third and fourth down.
“Our record isn't what we want to be,” head coach Dabo Swinney said. “But when you see the resilience, you know what these guys have under the hood.”
The Tigers are led by senior QB Cade Klubnik, who has completed 67.9 percent of his passes for 2,136 yards with 14 TDs and five INTs. He has performed much better in his last four starts, completing 77.8 percent of his passes for 1,140 yards, eight touchdowns, and one interception, with two rushing scores. Leading receiver Bryant Wesco Jr. is out for the season, vaulting sophomore T.J. Moore (31 receptions for 536 yards and four TDs) into the WR1 spot. Senior RB Adam Randall (116 carries for 570 yards and six TDs) paces the Clemson ground game.
The Tigers score 27.9 points per game (70th) and average 409.3 total yards (53rd), including 288.4 passing yards (16th) and 120.9 rushing yards (112th). The Clemson defense allows 22.4 points (51st) and 351.3 total yards (51st) per game, including 245.1 passing yards (105th) and 106.2 rushing yards (19th).
Clemson Tigers Football Injury Report: RB Jay Haynes (knee) is questionable. He has been sidelined since suffering a torn ACL in the 2024 ACC Championship.
Louisville lost a heartbreaker last week
Louisville (7-2 SU, 3-6 ATS, and 5-4 O/U) lost 29-26 in overtime at Cal last Saturday. The Cardinals are in the mix for a College Football Playoff spot, but the loss was costly. With Virginia's loss to Wake Forest last week, the Cards will drop below the Cavaliers in the rankings, as UVA won the head-to-head matchup earlier this season.
Cal went for the win on fourth down in OT, walking off the home team after the Cardinals settled for a field goal with their first possession of the extra period. The Golden Bears outgained the Cards 427-351 and made life difficult for Louisville QB Miller Moss, who was 20-for-38 passing with an interception.
“Disappointing loss,” coach Jeff Brohm said. “This one stings and hurts; it’s supposed to. We’ve got a lot of things that we got to, that I can go back and work on and find a way to get better.”
The USC transfer Moss leads the Louisville offense. The senior has completed 63.8 percent of his passes for 2,132 yards with 11 touchdowns and seven interceptions. He has thrown one pick in six of his last seven games and has completed less than 60 percent of his passes in two of the last three. Moss' top receiving targets are senior WRs Chris Bell (62 receptions for 792 yards and six TDs) and Caullin Lacy (48 receptions for 482 yards and two TDs). With leading rusher Isaac Brown (91 carries for 782 yards and five TDs) sidelined with a leg injury, the Cardinals will lean on sophomore RB Keyjuan Brown (66 carries for 457 yards and six TDs).
Louisville scores 37.0 points per game (16th) and averages 451.6 total yards (23rd), including 277.4 passing yards (25th) and 174.3 rushing yards (50th). The Cardinals' defense allows 24.4 points (69th) and 333.9 total yards (43rd) per game, including 211.6 passing yards (57th) and 122.3 rushing yards (32nd).
Louisville Cardinals Football Injury Report: LB Stanquan Clark (leg) is questionable. The All-ACC defender has been out since Week 2. Isaac Brown (leg) is not expected to play.
Clemson vs. Louisville Pick and Preview
Spread Pick for Clemson vs. Louisville
- Louisville -3 (4 Units)
The Cardinals are 5-2 straight-up after a loss under Brohm, with a win over Miami earlier this season as 10.5-point underdogs. I believe they'll bounce back to win and cover the three-point spread against a Tigers team that has lost two of their last three. The Cards upset the Tigers as 10.5-point dogs last season, but they're the better team in 2025.
The home team can pound the rock on the ground with Keyjuan Brown, who rushed for 136 yards on 14 carries (9.7 YPC) last weekend, and move the ball through the air against a weak Clemson pass defense. The Tigers have allowed 88 passing plays of ten-plus yards and seven of 40-plus yards this season. On the other side of the ball, the visitors have struggled to run the football, which will put pressure on Klubnik. Louisville's defense ranks 14th nationally in EPA allowed per drop back and ranks 18th in passing plays of ten-plus yards allowed.
Over/Under Pick for Clemson vs. Louisville
- Under 50 (4 Units)
I have concerns about both offenses and believe the defenses will hold up enough to keep the total from exceeding 50 points. Louisville will lean on its run game, but Clemson is stout against the run. While I'm confident the Cardinals' backs will wear down the Tigers throughout the game, creating some big plays in the second half, it won't come easily. Given how inefficient and turnover-prone Moss has been passing the football recently, I don't anticipate a high-scoring show by the home squad. On the other end of the field, Louisville's ball-hawking DBs (seventh-most interceptions) will get Klubnik out of rhythm. The Cardinals' pass rush has been solid (19 sacks), too. Without a reliable complementary run game, Clemson's QB will revert to the inconsistent play that marred him earlier in the season.
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