James Madison vs. Louisville Prediction and Picks for Friday, September 5, 2025
Week 2 of the 2025 college football season will open with the Louisville Cardinals hosting the James Madison Dukes, and we'll preview the lines and odds in our JMU vs. Louisville prediction. Both teams are 1-0 after handling lower-level opponents in Week 1 – JMU won 45-10 at home against Weber State, while Louisville won 51-17 at home against Eastern Kentucky. Kickoff is set for 7:00 PM ET on Friday, September 5.
If you're struggling to pick winners, you've come to the right place. We have the strongest NCAAF Predictions.
Can Dukes Start Hot Again?
In 2024, under first-year head coach Bob Chesney, the James Madison Dukes started their season 4-0 against a slate of Charlotte (30-7), Gardner-Webb (13-6), North Carolina (70-50), and Ball State (63-7). With a 45-10 win over FCS Weber State, the Dukes have taken the first step to starting 2025 on a similar note.
Alonza Barnett III, a fourth-year player and two-year starting quarterback at JMU, ran in the first touchdown of the game in the first quarter. He finished with only 14 completions on 22 passing attempts for 130 yards and a touchdown, but the Dukes rotated their quarterbacks liberally in the game from the first drive. Matthew Sluka, a sixth-year quarterback who started under Chesney at Holy Cross and transferred to JMU ahead of this season, finished the game with four pass attempts, six rush attempts, 45 yards from scrimmage, and two total touchdowns. By the end of the game, freshman quarterback JC Evans had also taken snaps and logged a rushing touchdown.
While the quarterback shuffle from Week 1 isn't likely to repeat itself – Barnett attempted 355 of 382 passes for the Dukes in 2024 – the team will hope their dominance on the ground against Weber State translates against Louisville. George Pettaway and Wayne Knight combined to run for 188 yards and a touchdown on 11 carries, leading a unit that finished with 313 yards on the ground – ranking them sixth among Division I teams in rushing yards per game. We'll find out on Friday, at least in part, whether that was a product of the Dukes' offense or their lesser Week 1 competition.
Sign Up for StatSalt News Alerts, Get Free Picks and Discounts
Subscribe Now
Louisville Rolls EKU in Week 1
The Louisville Cardinals easily took care of business in Week 1, dispatching the visiting FCS Eastern Kentucky Colonels by a score of 51-17. Isaac Brown put the first touchdown on the board with a 31-yard run in the first quarter; by the time EKU got on the board at the end of the first half, Brown had already run for two touchdowns and over 100 yards to put Louisville up 41 points.
For the most part, the Cards' offense was dominant in Week 1 – they gained 542 yards overall, ranking them 14th among Division I teams on a per-game basis. Brown, who finished the game with an absurd 126 yards and two touchdowns on only six carries, will likely get a longer run in what figures to be a closer game against the Dukes. The passing game wasn't quite as exceptional, with Miller Moss and Brady Allen combining to throw three interceptions to the Colonels' defense. Moss' interception-turned-touchdown by Colonels' defensive back Vito Tisdale is how EKU got on the scoreboard in the final minute of the first half. While the second interception bounced off the intended receiver and is hard to pin on Moss, it ended an otherwise-solid first-half performance on an annoyingly sour note. Moss finished the half having completed 17 of 25 passes for 223 yards and a touchdown before resting the remainder of the game; he'll likely get the full run against JMU on Friday.
The Cardinals are in their third year with head coach Jeff Brohm, who opened his tenure at Louisville with a 10-4 campaign and led the team to 9-4 in 2024. In 2023, the Cards opened the season 6-0 before a 21-38 loss to Pittsburgh in conference play. In 2024, they opened 3-0 before losing to Notre Dame, a team that remains nominally independent but participates in the ACC for non-football sports and has six ACC opponents on their 2025 schedule. Since Brohm's arrival, the Cardinals' only other regular-season loss to a non-conference opponent is their 31-38 loss to rival Kentucky at the end of the 2023 season.
Louisville -13.5 (-110) (4 Units)
Isaac Brown's dominant showing against EKU last week didn't come out of nowhere – the second-year back finished his 2024 true freshman campaign at Louisville with 1,173 yards, a 7.1 yard-per-carry average, 12 total touchdowns, and multiple annual ACC awards. If he stays in the Cards' lineup down to the wire in this game, he's liable to take any given clock-burning run in the fourth quarter for 40 extra yards and six extra points. Unless the Dukes' offense can go blow-for-blow with the Cards in a high-scoring game, I'd take Louisville to cover – they'll gain steam and pull away if given enough time.
Over 56.5 (-110) (5 Units)
The Cardinals have scored at least 31 points in their last eight games, dating back to a 45-52 loss against Miami in 2024. The Team Total Over is 7-3 in their last ten games, a stretch through which they've allowed at least 30 points to four of their opponents and at least 20 points to eight of them. On the Dukes' side, they've hit the 20-point threshold on offense in eight of their last nine games and given up 30+ points to three of their last five opponents. Even if these teams try to turn this game into a ground-out affair, their respective run games can still be good enough to turn this into a high-scoring contest.
Up To $1500 in Bonus Bets Paid Back if your First Bet Does Not Win
Bet $5 & Get $150
