Louisville vs Ole Miss NCAAF Week 1 Preview and Prediction September 6, 2026

Opening Betting Odds

Spread: MISS -6.5, LOU +6.5
Moneyline: MISS -250, LOU +215
Total: 55.5

LOU vs MISS Betting Preview

The Rebels are coming off their first ever appearance in the College Football Playoffs, and they defeated Tulane and Georgia before being eliminated by Miami in the Semi Final. Lane Kiffin left the team before the Playoffs started, signing a $91 Million Dollar contract to become the next head coach of the LSU Tigers.

They will play Louisville at a neutral site in Nashville in their season opener, and they are favored by about a touchdown. Louisville won nine games last year, and the highlight of the season was a 24-21 win at Miami as a double digit underdog.

This may look like a mismatch on paper, but it would be ill advised for the Rebels to take the Cardinals lightly.

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Louisville Betting Preview

• Head coach: Jeff Brohm
• Offensive coordinator: Brian Brohm
• Defensive coordinator: Mark Ivey
• 9-4 Overall in 2025
• 4-4 in the ACC in 2025
• 4-9 ATS in 2025

The Cardinals were 9-4 last season, but they were on the wrong side of a pair of overtime games, and they lost to Clemson by just one point. The only loss by more than a field goal was a game at SMU that starting quarterback Miller Moss missed due to injury.

Jeff Brohm brings in a new quarterback via the transfer portal from Ohio State. He was a four star recruit that has been gaining experience at one of the top programs in college football since 2023. While he didn’t see the field a lot with the Buckeyes, based on Brohm’s success developing quarterbacks you would expect him to do big things at Louisville. The Cardinal brought in transfers at wide receiver from Florida State and Vanderbilt.

On the defensive side of the ball they return four starters from a unit that ranked third in the ACC allowing just 20.5 points per game last season. They will have one of the top linebacker corps in the conference.

Ole Miss Betting Preview

• Head coach: Pete Golding
• Offensive coordinator: John David Baker
• Defensive coordinator: Patrick Toney
• 13-2 Overall in 2025
• 7-1 in the SEC in 2025
• 9-6 ATS in 2025

Pete Golding takes over for Lane Kiffin, and he comes into the 2026 season with a pair of Playoff wins on his resume. That’s two more than Kiffin.

Trinidad Chambliss might be the best quarterback in the SEC, and he was the leading passer in the SEC with just shy of 4,000 yards in 2025. Kewan Lacy returns after finishing second in the SEC in rushing with 1,567 yards and 24 touchdowns last season.

The defense is full of incoming transfers, and will have the talent in place to be better than they were a year ago. The jury is still out, but the loss of Lane Kiffin might be more of a positive than a negative when all is said and done.

Relevant Trends:

• Ole Miss is 8-2 in their last 10 overall.
• Jeff Brohm is 12-17 in his career vs ranked teams.
• Ole Miss is 10-0 in their last 10 vs unranked teams.
• Louisville is 2-5 in their last 7 vs ranked teams.
• The Under is 5-2 in Louisville’s last 7 vs ranked teams.

PREDICTION: Louisville 27 – Ole Miss 31

While we expect this to be a close game in the end, it might take a while to get the new quarterback in a new system up to speed. Given that Ole Miss has the edge when it comes to continuity on offense, it might be a better bet to take the Rebels for the first half rather than the full game. Keep in mind that the Cardinals upset Miami last year and if you throw out the game that their quarterback didn’t play, they never lost by more than three points. Sign up for account at BetOnline and take advantage of reduced juice offers and a juicy sign up bonus.

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