Louisville Cardinals vs Pittsburgh Panthers Prediction, 9/27/2025 College Football Picks, Best Bets & Odds

Game: Louisville Cardinals vs Pittsburgh Panthers

Date: Saturday, September 27, 2025

Location: Acrisure Stadium in Pittsburgh, PA

TV: ESPN2

Odds/Point Spread: Panthers (+3.5)

Total/Over-Under: 56

The Louisville Cardinals (3-0) are en route to Acrisure Stadium on Saturday, September 27, 2025 where they will play the Pittsburgh Panthers (2-1). Louisville opens this contest as 3.5-point favorites. The betting total comes in at 56.

The Louisville Cardinals step onto the field holding a record of 3-0 for this season. The last time they stepped onto the field, the Cardinals took the field against the Bowling Green Falcons and notched a win by a score of 40-17. When all was said and done, they had 62 plays which converted into 439 yards. The Louisville Cardinals ended up rushing 29 different times and totaled 126 yards, which came out to an average of 4.3 yds per attempt. When it came to stopping the run, the Cardinals conceded 190 yds on 29 tries, which is 6.6 yds per rush allowed. Louisville relinquished 11 completions on 21 attempts for 131 yards, and a completion percentage of 52.4%.

When it comes to putting the ball in the endzone, the Louisville Cardinals hold an average of 39.7 PPG. As a team they're averaging 156.0 yards on the ground ranking this team at 76th in college football. The Cardinals have earned 1,245 total yards this year. When it comes to distribution of touchdowns, Louisville has totaled 3 touchdowns through the air and 8 touchdowns on the ground. Louisville has 61 1st downs as a team, and they have been flagged for 23 infractions for 210 yards. They have surrendered the football 5 times.

In terms of passing yardage, the Cardinals have conceded 344 yards which has them sitting in 4th in the country. They have allowed 114.7 yards per game through the air as well as conceding a completion percentage of 51.4%. Over the course of this season, they have relinquished 244.7 yards per outing which puts them 16th in the country. They have conceded 2 touchdowns by air and 3 touchdowns pounding the rock. Opposing teams are running for an average of 3.4 yards per rushing attempt and 130.0 rushing yards per contest for the campaign. In total, they have conceded 390 yards via the running game in 3 contests. The Cardinals are ranked 29th in the country in terms of their opponents scoring, allowing 16.0 PPG.

Get all of our College Football Picks

The Panthers head into this matchup 2-1 for this season. For their last game, the Panthers took a loss by a score of 31-24 when they played the West Virginia Mountaineers. Pittsburgh relinquished 58 rushing attempts for 174 yds (3.0 yards per rush). The Panthers passing defense allowed a completion rate of 68.8%, relinquishing 260 yds on 22 out of 32 passing. The Panthers finished the contest with a total of 349 yds and they ran 72 plays (4.8 yds per play). Pittsburgh rushed the football for 1.4 yards per carry, totaling 46 yds on 34 attempts.

The Pittsburgh Panthers have an average of 424.3 yards/outing, which is good for 53rd in Division 1. The Pittsburgh offense has accrued 216 yds of penalties on 23 infractions, which is good for 67th in the country in terms of giving up free yards. They average 109.3 yards per game on the ground and have toted the ball for 328 yards overall. They have thrown 3 picks while conceding 0 fumbles and they have been able to tally 58 first downs. In terms of their ability to score points, the Panthers are 17th in college football holding an average of 43.3 PPG. During this campaign to this point, the Panthers have thrown for a total of 945 yards through the air along with holding an average of 315.0 passing yards per outing, which is ranked 19th in Division 1.

Pittsburgh has conceded a total of 243 yards on the ground (81.0 yards per outing) in addition to 4 touchdowns via the rush for the season. They have yielded 3 touchdowns via the pass in addition to 202.7 yards per contest, which puts them in 64th in college football. This year, they have allowed 57 total points. Their defense has totaled 1 fumble recovered and 2 interceptions on the year. The Panthers defense has taken part in 216 plays, which is 40th in college football. The Panthers are giving up 19.0 PPG, which has them ranked 45th in the country.

Who will win tonight's Cardinals/Panthers college football game against the spread?

Josh's Pick: Take the Cardinals -3.5

Get $60 worth of FREE premium member picks. No Obligation. No Salesman. No Credit Card. Fast Sign up with Instant Access Click Here