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Pittsburgh Panthers vs Louisville Cardinals September 27th 2025
The Louisville Cardinals head to Acrisure Stadium to take on the Pittsburgh Panthers in Week 5 of the 2025 regular season. The game is set for Saturday, September 27, at 12:00 PM and will air on ESPN2. Both teams are part of the Atlantic Coast Conference, making this a key conference game.
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Louisville enters the game with a perfect 3-0 record, having won all their games at home. Pittsburgh, on the other hand, stands at 2-1, with both wins at home. The Panthers look to defend their home turf, while the Cardinals aim to continue their winning streak on the road.
Louisville vs Pittsburgh CFB Key Information
- Sport: College Football
- Teams: Louisville Cardinals vs. Pittsburgh Panthers
- Venue: Acrisure Stadium in Pittsburgh, PA
- Date: Saturday, September 27, 2025
- Betting Odds: Louisville Moneyline -191, Pittsburgh Moneyline +159, Louisville Spread -4.5 (-111), Pittsburgh Spread +4.5 (-109), Total Over 57.5 (-114), Total Under 57.5 (-107)
Louisville vs Pittsburgh Week 5 Betting Preview
Louisville travels to Pittsburgh on Saturday, Sept. 27 at noon ET (ESPN2). The Cardinals are 3-0 after beating Bowling Green 40-17, while the Panthers are 2-1 coming off a bye. This is Louisville’s first ACC matchup of 2025 and their first test against a Power 4 opponent.
The teams split their last two meetings, with Louisville winning 37-9 in 2024 and Pitt handing the Cardinals a 38-21 loss in 2023.
Line Movement and Odds
Louisville opened as a 4.5-point favorite. The line has held at Louisville –4.5 with a total of 57.5 at most college football odds boards. Current moneyline: Louisville –182, Pittsburgh +150.
Public money leans to the Cardinals, while sharps have shown light interest in the over. Louisville is 4-9 ATS in its last 13 games. Pitt is 10-2 ATS in its last 12 at home.
Matchup Breakdown
Louisville outlook
Quarterback Miller Moss leads an efficient passing game with 777 yards this year. Running back Isaac Brown has 248 yards but is questionable with a leg injury. Without him or Duke Watson, Louisville could lean on Moss more. The defense ranks top 10 nationally in sacks and interceptions, giving them a chance to disrupt any offense.
Pittsburgh outlook
Quarterback Eli Holstein has thrown for 822 yards and nine touchdowns. Raphael Williams Jr. is his top target with 285 yards and three scores. Pitt’s defense is top 10 in sacks and excels at recovering fumbles. If their secondary holds up, they can limit Moss and pressure Louisville into mistakes.
Key battle
Louisville’s shorthanded backfield versus Pitt’s defensive front. If the Cardinals cannot establish the run, it will be on Moss to carry the offense against one of the ACC’s best pass-rush units.
Injuries and Conditions
Louisville Cardinals (injury report)
- RB Isaac Brown, questionable (leg)
- RB Duke Watson, questionable (leg)
- LB S. Clark, out (ankle surgery)
- WR Chris Bell, questionable (undisclosed)
Pittsburgh Panthers (injury report)
- RB D. Reid, questionable (lower body)
- TE J. Overman, questionable
- CB R. Battle, questionable
- CB T. Lynum, questionable (leg)
Best Bets and Prediction
Our projection: Louisville 35, Pittsburgh 28. That leans to the over 57.5 and covers the 4.5-point spread.
- Best bet: Louisville –4.5
- Secondary lean: Over 57.5
ATS trends favor Pitt at home, but Louisville’s pressure defense and Moss’s arm give them the edge.
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