Louisville football opened the 2025 season with a 51–17 rout of Eastern Kentucky. On paper, it was a commanding win, but from a betting perspective, it left something to be desired. The Cardinals were 37.5-point favorites and failed to cover, largely because they didn’t force a single turnover and let the Colonels sneak in late points once the starters sat. For gamblers, winning without covering often feels like a letdown.
Now the competition stiffens. In Week 2, Jeff Brohm’s team faces James Madison, one of the most consistent Group of Five programs of the past decade. The Dukes went 11–2 last year and bring a physical rushing attack that will test Louisville’s front seven. The Cards are 14.5-point favorites, but that number feels dangerous given JMU’s track record of hanging tough in these kinds of games.
The value lies in totals and props for Louisville fans because one thing feels certain, and that is that there will be a lot of points. Here are the three best bets for tonight’s matchup.
3 best bets against James Madison
1. Louisville over 34.5 points (-128, FanDuel)
The Cardinals showed in Week 1 that they can score in bunches. Miller Moss looked poised in his first start, and the offense scored touchdowns on its first four drives, rarely facing third down. With Isaac Brown picking up where he left off last year and Louisville’s tempo under Brohm forcing defenses to play on their heels, this unit has the tools to light up the scoreboard again. Sure, James Madison is a step up from EKU, but unless JMU’s front can consistently win at the line, Louisville should clear 34.5 comfortably.
2. 1st half O 28.5 points (+102, FanDuel)
As stated above, the Cards should come out firing again, but don’t overlook JMU’s ability to contribute. The Dukes boast one of the country's deeper backfields with George Pettaway and Wayne Knight, both of whom are capable of ripping off chunk plays. Louisville’s defense, while improved, is still working in multiple transfers and has yet to prove it can consistently stop the run. James Madison will most likely run the ball early, then use a play-action or deep pass play to surprise Louisville and score once or twice in the 1st half. That dynamic sets up perfectly for a high-scoring first half. The first 30 minutes should be a back-and-forth stretch with plenty of fireworks—more than enough to hit this over.
3. Isaac Brown 1st TD (+290, FanDuel)
If it ain’t broke, don’t fix it. Brown cashed this ticket in Week 1, and in 2024, this bet cashed in 4 games. There were an additional two games where the opposing team scored first, but Isaac Brown scored the first Louisville touchdown. Brohm leans on him heavily in red-zone situations because of his blend of vision and burst. At +290, the value is too good to pass up for a player who’s consistently the first option when Louisville gets near the goal line. Even if it’s just a half-unit, this bet feels smart.
Related: Louisville vs James Madison final odds and predictions
Best Bets Recap: FanDuel
Louisville Team Total Over 34.5 (-128)
1st Half Over 28.5 (+102)
Isaac Brown First Touchdown (+290)