James Madison vs Louisville Prediction, Pick & Odds (Friday, Sep. 5)

• Louisville hosts upset-minded James Madison Friday night in a non-conference clash at 7 p.m. on ESPN2
• The Dukes are two-touchdown underdogs, but have notched wins over ACC foes Virginia and North Carolina the last two years.
• Check out my James Madison vs Louisville prediction and pick, plus the best odds for this Friday night CFB clash

A pair of 1-0 teams collide tonight at L&N Stadium in Louisville when the Cardinals host James Madison. Kickoff is set for 7:00 pm ET, with ESPN2 carrying the broadcast.

Neither team had any trouble in their season opener. JMU, a member of the Sun Belt, is 2-1 against ACC teams since joining the FBS, and is 4-10 all-time against ACC squads. This will be the school’s second meeting.

James Madison has pulled big upsets before. I have everything you need to know for tonight, including my prediction, pick and insight on the best lines as we start digging into the Week 2 NCAAF public betting splits.

James Madison vs Louisville Odds

The Dukes are 1-0 against the spread this season after spanking Weber State 45-10. Louisville is 0-1 against the spread, but it’s close; the Cards beat Eastern Kentucky 51-17, and the spread was right around 38 points, so if you had the right sportsbook, you made out. Both teams mashed the over.

Last season, James Madison went 7-6 against the number, and Louisville was 6-7.

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Odds as of Sept. 5 at FanDuel. Grab our FanDuel promo code to get a big bonus for James Madison/Louisville.

The spread has shifted in the Cardinals’ favor. It’s either 14 or 14.5 points. The total is a firm 55.5. The best moneyline odds are at FanDuel for James Madison at +460 and at BetMGM for Louisville at -600.

Each of Louisville’s last eight games against non-conference schools have hit the over, and the Cardinals have covered the spread in seven of their previous eight September games as a home favorite.

But remember, teams usually play plenty of cupcake teams in September to get the season rolling.

James Madison vs Louisville Prediction

• Winner Prediction: Louisville

James Madison won’t be intimidated by an ACC school, and I love taking them and the points, but I don’t see them winning this game straight up. Louisville should be able to get some production out of star running back Isaac Brow, who had 126 yards on six, yes, six, carries in the Week 1 win. Louisville put up 542 yards total. Moss threw for 223 yards in the first half, but also two picks.

The gap between good Sun Belt/Group of Five schools and ACC schools isn’t as big as people think. James Madison has proved that. Louisville might be better than UNC and Virginia were, but James Madison has shown they can play with the big boys.

James Madison vs Louisville Picks

• James Madison +14.5 (-118 at FanDuel)

• Over 55.5 (-106 at FanDuel)

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James Madison is a great get the higher this number goes. The last two seasons, James Madison has started the same way. In Week 1, they played a patsy and crushed them, then they played a nearby ACC school.

They’ve pulled upsets each time, edging Virginia in 2023 and basically ending Mack Brown’s career at North Carolina with a 70-50 win in 2024. Before bumping up to FBS, James Madison was an FCS power.

The Dukes return quarterback Alonza Barnett III, who had 33 total TDs last season. He tore his ACL late in the season, but recovered and played in the win over Weber State. He’s your standard dual threat.

Louisville brought in transfer Miller Moss from USC to play QB. He was the big thing for a hot minute with the Trojans, but when USC was 4-5 with him as a starter, he was benched. Did he stick things out and try to improve? No way. He bolted for Louisville and QB guru Jeff Brohm.