The Louisville Cardinals (3-0) will face the Pitt Panthers (2-1) at Acrisure Stadium on Saturday afternoon. Louisville enters the contest as a favorite on the road, looking to stay undefeated on the season. This matchup marks the start of conference play for both teams, and both teams will look to get a win in their first ACC game of the season. Before the action begins in Pittsburgh, continue reading to get my Louisville vs Pitt prediction.
Our Louisville vs Pitt Pick
- Pick: Pitt +5.5
- Confidence: 3/5
Game Snapshot
- Matchup: Louisville Cardinals vs Pittsburgh Panthers
- Date & Time: Saturday, September 27, 2025, 12:00 PM ET
- Venue: Acrisure Stadium, Pittsburgh, PA
- Broadcast: ESPN2
Louisville vs Pitt Odds
| Betting Line | Louisville | Pittsburgh |
|---|---|---|
| Spread | -5.5 | +5.5 |
| Moneyline | -200 | +170 |
| Total | 58.5 | |
Key Storylines
Louisville’s Road Performance: Louisville has struggled in road games against Pittsburgh, holding an 0-3 record at Acrisure Stadium since joining the ACC in 2014. But the Cardinals have shown improvement under head coach Jeff Brohm. The Cardinals have a perfect 3-0 record this season, with all three wins coming by double-digits.
Pittsburgh’s Bye Week: The Panthers are coming off a bye week following a 31-24 overtime loss to West Virginia in the Backyard Brawl. This extra preparation time could benefit Pittsburgh and will allow them to recuperate after playing their rivalry game with the Mountaineers.
Quarterback Play
Louisville: Quarterback Miller Moss has been efficient this season for Louisville. He has thrown for 690 yards with two touchdowns and two interceptions. He leads an offense averaging 39.7 points per game, though the Cardinals have faced weaker competition so far this year.
Pittsburgh: Eli Holstein has been impressive for Pitt. He has passed for 822 yards with nine touchdowns and three interceptions. His ability to stretch the field vertically will be important for Pittsburgh’s success against Louisville’s defense.
Betting Trends & H2H
- Louisville is 3-0 straight up but they are 0-3 against the spread to start the season.
- Pitt has covered the spread in two of their first three games this year.
- Both teams have had two of their first three games go over their totals.
- Pitt is 11-10 all-time against Louisville. Louisville has lost three straight road games against the Panthers.
Louisville vs Pitt Model Projection
Score Projection: Louisville 31 – Pittsburgh 28
Win Probability: Louisville 57%, Pittsburgh 43%
Final Thoughts
I think that we are in for a very close game in Pittsburgh on Saturday afternoon. The Panthers and Cardinals can both move the ball effectively through the air, but I think that Eli Holstein is being underrated a bit in the betting markets ahead of this game. I’ll take the points with Pitt here, as they should be able to keep this game close and potentially win it outright.
