ACC foes meet when the Louisville Cardinals (3-0) and the Pittsburgh Panthers (2-1) square off on Saturday, September 27, 2025 at Acrisure Stadium.

The Cardinals are favored, but by less than a touchdown (-3.5), versus the Panthers. The over/under for this game is 55.5 points.

Keep reading for our betting preview for this this contest between the Cardinals and the Panthers, and find all of our betting picks here, too!

Louisville vs. Pittsburgh betting lines

• Spread favorite: Cardinals (-3.5)
• Moneyline: Cardinals (-175), Panthers (+144)
• Total: 55.5 points
• TV Channel: ESPN2
• Live Stream: Fubo

Louisville vs. Pittsburgh betting info and stats

Louisville has yet to win a game against the spread so far this season (0-3-0). Louisville is winless ATS (0-3) when favorites by at least 3.5 points. Louisville has been named as moneyline favorites three times this season, and has put together a 3-0 record in those outings. Pittsburgh, through three games with a set spread this season, has gone 2-1-0 against the spread. This will be the first game on the year Pittsburgh is an underdog on the moneyline.

Louisville vs. Pittsburgh key players

Louisville Cardinals

• Miller Moss has recorded 690 yards (230.0 ypg) on 53-of-80 passing with two touchdowns compared to two interceptions this season.
• The team’s top rusher, Isaac Brown, has carried the ball 19 times for 248 yards (82.7 per game), scoring three times.
• Keyjuan Brown has collected 110 yards on 22 attempts, scoring three times. He’s grabbed four passes for 47 yards (23.5 per game), as well.
• Chris Bell’s leads his squad with 197 yards as a receiver. He’s racked up that yardage on 13 catches (out of 24 targets) and scored one touchdown.
• Caullin Lacy has caught 14 passes while averaging 57.0 yards per game.
• Dacari Collins has compiled six receptions for 105 yards, an average of 52.5 yards per game.
• Clev Lubin, the team’s tackle and sacks leader, has collected 3.5 sacks, 2.0 TFL and 19 tackles.
• D’Angelo Hutchinson leads the team with one interception, while also recording 16 tackles, 1.0 TFL, and one pass defended.

Pittsburgh Panthers

• Eli Holstein has put up 822 passing yards, or 274.0 per game, so far this season. He has completed 65.9% of his passes and has collected nine touchdowns with three interceptions. He’s also chipped in on the ground with 16.7 rushing yards per game while scoring as a runner one time.
• Desmond Reid has rushed for 142 yards on 24 carries so far this year while scoring one time on the ground. He’s also added six catches, totaling 71 yards.
• Juelz Goff has racked up 84 yards (on 21 attempts) with two touchdowns.
• Raphael Williams has racked up 285 receiving yards on 13 receptions to pace his squad so far this season while scoring three touchdowns as a receiver.
• Bryce Yates has caught four passes and compiled 143 receiving yards (71.5 per game) with one touchdown.
• Kenny Johnson’s eight catches (on 16 targets) have netted him 86 yards (28.7 ypg) and one touchdown.
• Kyle Louis has 2.0 sacks to lead the team, and also has 4.0 TFL, 19 tackles, and one interception.
• Pittsburgh’s leading tackler, Rasheem Biles, has 28 tackles and 2.0 TFL this year.
• Braylan Lovelace has picked off a team-leading one pass. He also has 17 tackles and one pass defended to his name.