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Louisville vs Pittsburgh Prediction 9/27/2025 Today’s College Football Picks
Pick details
Louisville (3-0) vs Pittsburgh (2-1)
September 27, 2025 at 12:00 PM EDT
The Line: Betting Odds: Pittsburgh +4.5 — Over/Under: +56.5
The Louisville Cardinals and the Pittsburgh Panthers meet Saturday in college football action from Acrisure Stadium. Here’s a Louisville vs Pittsburgh prediction. We will look at this from a betting perspective and determine the best Louisville vs Pittsburgh pick. We will examine:
The Louisville Cardinals recent form and player performance
The Pittsburgh Panthers recent form and player performance
Recent betting trends and streaks involving the Louisville Cardinals
Recent betting trends and streaks involving the Pittsburgh Panthers
Recent betting trends in games played between Louisville and Pittsburgh
A summary that ties it all together and produces a favorable betting outcome for the Louisville vs Pittsburgh game
The Cardinals only have three games completed so far this year, but things have been going quite well overall. Louisville kicked things off with a matchup against Eastern Kentucky, eventually taking a blowout win 51-17. Game two against James Madison was closer but still a two-score victory, as Louisville scored twice in the fourth quarter to cap off a 28-14 victory. The Cardinals offense accounted for a tepid 264 yards (151 passing) in that one, with 5.0 yards per play, 12 first downs and a sketchy 5-of-14 rate on third-down tries.
Last weekend versus Bowling Green, Louisville posted 21 points in the first half and 19 more after the break along the way to a 40-17 win. QB Miller Moss was 23-of-32 for 316 yards in the victory, and Keyjuan Brown topped the rushers with 12 carries for 84 yards and two scores. Caullin Lacy had eight catches for 97 yards to lead the receivers in the win.
Over on the Pittsburgh side, they’ve got three games in the bag this year as well, notching a 2-1 run in those outings. The Panthers didn’t have any issues with Duquesne in their opener, rolling to a 61-9 blowout win. Game two against Central Michigan wasn’t too much trouble either, as Pittsburgh scored 17 points in the second quarter and 14 more in the fourth on the way to a 45-17 win. The Panthers defense held the Chippewas to just 217 total yards in the win alongside 3.2 yards per play and only 13 first downs.
Matched up against West Virginia in their most recent outing, the Panthers took their first loss of the year. After outscoring the Mountaineers 21-17 in the second half, Pitt ended up losing in overtime 31-24. QB Eli Holstein finished 22-of-37 for 303 yards, one TD and one pick. Juelz Goff carried eight times for a team-high 37 rush yards, and Raphael Poppi Williams caught six balls for 119 yards and a touchdown.
Heading into Week 5, Raphael Williams Jr. leads Pittsburgh for touchdowns (3) this season.
Heading into Week 5, Isaac Brown ranks 1st amongst qualified players for Yards Per Carry (13.1) this season.
Pittsburgh ranks T1st among FBS teams for Q1 opponent points per game this season (0.0).
Pittsburgh ranks 6th among FBS teams for Q4 points per game this season (12.3).
Louisville ranks 4th among FBS teams for passing yards allowed per game this season (114.7).
Louisville ranks T7th among FBS teams for red zone percentage against this season (60.0).
I’m going to stay with Louisville, though you could make a case either way. The Cards did a good job on defense last weekend versus Bowling Green, giving up 321 yards (131 passing), 14 first downs and 4-of-12 on third-down tries alongside a couple of interceptions. The offense posted 439 yards (313 passing) on the other side with 7.1 yards per play but mustered just 4-of-11 on third downs themselves. The good news is that Louisville has scored at least 28 points in all three games this year, and 40 or more in two of those.
As for Pitt, they’ve had a bit of extra time to stew on that tough road loss to West Virginia. The Panthers went just 4-of-17 on third downs and had only 46 rushing yards in that one, and the 14 penalties for 118 yards didn’t help matters either. The defense held strong on third downs themselves (5-of-17) but did get burned by flags and the rush (174 yards). In any case, Pitt should be ready for this matchup, and it should be a fun one to check out. I like Louisville a little better but it’s a coin flip.
The Louisville Cardinals recent form and player performance
The Pittsburgh Panthers recent form and player performance
Recent betting trends and streaks involving the Louisville Cardinals
Recent betting trends and streaks involving the Pittsburgh Panthers
Recent betting trends in games played between Louisville and Pittsburgh
A summary that ties it all together and produces a favorable betting outcome for the Louisville vs Pittsburgh game
Louisville Cardinals Betting Preview
The Cardinals only have three games completed so far this year, but things have been going quite well overall. Louisville kicked things off with a matchup against Eastern Kentucky, eventually taking a blowout win 51-17. Game two against James Madison was closer but still a two-score victory, as Louisville scored twice in the fourth quarter to cap off a 28-14 victory. The Cardinals offense accounted for a tepid 264 yards (151 passing) in that one, with 5.0 yards per play, 12 first downs and a sketchy 5-of-14 rate on third-down tries.
Last weekend versus Bowling Green, Louisville posted 21 points in the first half and 19 more after the break along the way to a 40-17 win. QB Miller Moss was 23-of-32 for 316 yards in the victory, and Keyjuan Brown topped the rushers with 12 carries for 84 yards and two scores. Caullin Lacy had eight catches for 97 yards to lead the receivers in the win.
Pittsburgh Panthers Betting Preview
Over on the Pittsburgh side, they’ve got three games in the bag this year as well, notching a 2-1 run in those outings. The Panthers didn’t have any issues with Duquesne in their opener, rolling to a 61-9 blowout win. Game two against Central Michigan wasn’t too much trouble either, as Pittsburgh scored 17 points in the second quarter and 14 more in the fourth on the way to a 45-17 win. The Panthers defense held the Chippewas to just 217 total yards in the win alongside 3.2 yards per play and only 13 first downs.
Matched up against West Virginia in their most recent outing, the Panthers took their first loss of the year. After outscoring the Mountaineers 21-17 in the second half, Pitt ended up losing in overtime 31-24. QB Eli Holstein finished 22-of-37 for 303 yards, one TD and one pick. Juelz Goff carried eight times for a team-high 37 rush yards, and Raphael Poppi Williams caught six balls for 119 yards and a touchdown.
Louisville Cardinals @ Pittsburgh Panthers Betting Trends: Week 5
Pittsburgh Panthers Player Prop Facts
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Heading into Week 5, Raphael Williams Jr. leads Pittsburgh for touchdowns (3) this season.
Louisville Cardinals Player Prop Facts
Heading into Week 5, Isaac Brown ranks 1st amongst qualified players for Yards Per Carry (13.1) this season.
Matchup/League Facts
Pittsburgh ranks T1st among FBS teams for Q1 opponent points per game this season (0.0).
Pittsburgh ranks 6th among FBS teams for Q4 points per game this season (12.3).
Louisville ranks 4th among FBS teams for passing yards allowed per game this season (114.7).
Louisville ranks T7th among FBS teams for red zone percentage against this season (60.0).
Louisville vs Pittsburgh Prediction
I’m going to stay with Louisville, though you could make a case either way. The Cards did a good job on defense last weekend versus Bowling Green, giving up 321 yards (131 passing), 14 first downs and 4-of-12 on third-down tries alongside a couple of interceptions. The offense posted 439 yards (313 passing) on the other side with 7.1 yards per play but mustered just 4-of-11 on third downs themselves. The good news is that Louisville has scored at least 28 points in all three games this year, and 40 or more in two of those.
As for Pitt, they’ve had a bit of extra time to stew on that tough road loss to West Virginia. The Panthers went just 4-of-17 on third downs and had only 46 rushing yards in that one, and the 14 penalties for 118 yards didn’t help matters either. The defense held strong on third downs themselves (5-of-17) but did get burned by flags and the rush (174 yards). In any case, Pitt should be ready for this matchup, and it should be a fun one to check out. I like Louisville a little better but it’s a coin flip.
