Louisville vs Pittsburgh Prediction 9/27/25 College Football Picks Today

In this article, we will formulate a Louisville vs Pittsburgh Prediction for this College Football Week 5 game on Saturday, September 27^th at the Acrisure Stadium. Let’s take a look at the prediction for this College Football matchup.

Pittsburgh Preview

Pittsburgh has a 2-1 record this season and are sitting on the 11th place of the ACC. They are 2-1 ATS, 2-1 in Over/Under and have a 2-0 home record and 0-1 away record. The Panthers are coming off a 24-31 away loss to West Virginia and are playing Louisville, Boston College and Florida State next.

Offensively, the Panthers average 43.3 points per game, which ranks 18th in the nation. Defensively, they allow 19.0 points per game, which is 45th. Pittsburgh averages 424.3 total yards per game, with 109.3 rushing yards and 315.0 passing yards per game. They allow 283.7 total yards per game, with 81.0 rushing and 202.7 passing yards per game.

Eli Holstein leads the Panthers with 822 passing yards and 65.9% completed passes. Desmond Reid leads the team in rushing yards, with 142, while Raphael Williams has a team-high 12 caught passes for 245 receiving yards, and has three touchdowns.

Defensively, Rasheem Biles has a team-high 30 total tackles, 6 of them solo. Francis Brewu leads the Panthers in sacks, with 2.0, while Kyle Louis has one interception.

Louisville Preview

Louisville has a 3-0 record this season and are sitting on the 9th place of the ACC. They are 0-3 ATS, 2-1 in Over/Under and have a 3-0 home record and 0-0 away record. The Cardinals are coming off a 40-17 home victory over Bowling Green and are playing Pitt, Virginia and Miami next.

Offensively, the Cardinals average 39.7 points per game, which ranks 29th in the nation. Defensively, they allow 16.0 points per game, which is 30th. Louisville averages 415.0 total yards per game, with 156.0 rushing yards and 259.0 passing yards per game. They allow 244.7 total yards per game, with 130.0 rushing and 114.7 passing yards per game.

Miller Moss leads the Cardinals with 690 passing yards and 66.3% completed passes. Isaac Brown leads the team in rushing yards, with 248, while Isaac Brown has a team-high 5 caught passes for 77 receiving yards, and has three touchdowns.

Defensively, Clev Lubin has a team-high 19 total tackles, 11 of them solo. Clev Lubin leads the Cardinals in sacks, with 3.5, while D’Angelo Hutchinson has one interception.

Louisville Cardinals @ Pittsburgh Panthers Betting Trends: Week 5

Why the Pittsburgh Panthers will win

• Pittsburgh has won 19 of its last 21 September home games against non-AP-ranked teams.
• Louisville has lost each of its last three games at Acrisure Stadium.
• Pittsburgh has covered the spread in each of its last four games as a home underdog.
• Louisville has failed to cover the spread in each of its last four games in Pennsylvania.
• Pittsburgh has won the first half in four of its last five home games against conference opponents.

Why the Louisville Cardinals will win

• Louisville has won each of its last 10 September games against non-AP-ranked teams.
• Pittsburgh has lost each of its last five games against conference opponents.
• Pittsburgh has failed to cover the spread in four of its last five games against conference opponents.
• Pittsburgh has lost the first half in four of its last five games against conference opponents.

Total Points Facts

• Each of Pittsburgh’s last 10 September home games against non-AP-ranked teams have gone OVER the total points line.
• Four of Louisville’s last five games have gone OVER the total points line.

Pittsburgh Panthers Player Prop Facts

• 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

In their previous meeting last season, Louisville won 37-9 at home, but Pittsburgh is 7-3 in their last 10 head-to-head meetings, having won their last five home meetings against Louisville. Under is 7-3 in their last 10 meetings.

In this Louisville vs Pittsburgh Prediction, Louisville is coming as -4.5-point road favorites, with the total set at 58 points. the Cardinals have won all of their games this season, but failed to cover the spread in each one. Pitt has been dominating Louisville at their home court, and they have won and covered each of their two home games this season. I like Pittsburgh as home dogs in this spot, so I’m going to grab the +4.5 with Pitt in this one.