Updated September 4, 2026
The Louisville Cardinals and Ole Miss Rebels open the season Sunday night with the only Top 25 matchup of Week 1. No. 24 Louisville will take on No. 9 Ole Miss at Nissan Stadium in Nashville, with kickoff set for 7:30 p.m. ET.
There’s plenty to watch in this one. Jeff Brohm has built a reputation for pulling off big upsets, and he’ll enter another season with a new quarterback in former Ohio State QB Lincoln Kienholz. On the other side, Heisman hopeful Trinidad Chambliss is back, but Ole Miss begins a new era under Pete Golding following Lane Kiffin’s departure.
In this preview, I’ll share my Louisville vs Ole Miss prediction and break down some of the biggest storylines heading into Sunday night.
I’m taking No. 9 Ole Miss to get it done Sunday night and win by a touchdown or more against a pesky Louisville team. You can currently get Ole Miss -6.5 at around 54¢ on Polymarket, and I think that’s a fair price for the Rebels in Nashville.
I expect Louisville to be a pretty popular upset pick, and I can’t blame anyone given Jeff Brohm’s track record when he's priced as an underdog. But I have no problem going against the grain here for a few reasons.
My biggest concern is Louisville’s offensive line. The Cardinals return just one starter up front in Lance Robinson, with transfers Eryx Daugherty, Johnnie Brown III, and Cason Henry among the new pieces. There’s plenty of experience there, but an almost entirely new offensive line may need some time to gel.
And this is a pretty brutal matchup to figure things out. Ole Miss should have one of the better defensive fronts Louisville sees all season, led inside by Will Echoles. That’s especially concerning with Lincoln Kienholz making his first career collegiate start at quarterback.
Then there’s the Brohm factor. He’s been excellent in games like this, including last year’s road upset of No. 2 Miami. But Louisville isn’t sneaking up on Ole Miss here. The Rebels should have their full attention on the Cardinals in an important first regular-season game for Pete Golding after taking over for Lane Kiffin and leading Ole Miss through last season’s College Football Playoff run.
That’s enough for me to lay the 6.5 points. I think Louisville keeps things competitive, but Ole Miss has enough of an advantage in the trenches to eventually create some separation.
Our ATS Quantitative Model for Louisville vs Ole Miss agrees, giving the Rebels a 56% chance to cover and a 4.8% model edge. It projects a 31-24 Ole Miss win, which would be just enough to cover the 6.5-point margin.
Trinidad Chambliss is back at Ole Miss for what has to be his final season of college football. After initially being denied another year of eligibility by the NCAA, Chambliss was granted a sixth year for the 2026 season following a February court injunction in Mississippi.
And that’s obviously huge news for the Rebels. Chambliss enters 2026 as one of the best quarterbacks in the country and a legitimate Heisman contender after throwing for 3,937 yards, 22 touchdowns, and just three interceptions last season. He completed 66.1% of his passes, averaged 8.8 yards per attempt, and added 527 yards and eight touchdowns on the ground.
He should be plenty motivated, too. Chambliss helped lead Ole Miss all the way to the College Football Playoff semifinals last season, where the Rebels came up just short in a 31-27 loss to Miami.
And Louisville can’t exactly sell out to stop Chambliss. Junior running back Kewan Lacy is back after rushing for 1,567 yards and 24 touchdowns last season, while adding another 177 yards through the air. He enters 2026 as one of the top running backs in the country in his own right.
With Chambliss and Lacy sharing the backfield again, Louisville will have its hands full trying to slow down an Ole Miss offense led by two of the best players in college football.
If there’s anyone you want coaching your team as an underdog, Jeff Brohm has to be on the short list. The former Louisville quarterback has made a habit of knocking off highly ranked teams, including a top-15 opponent in each of his first three seasons back with the Cardinals.
Louisville beat No. 10 Notre Dame 33-20 in 2023, went on the road and stunned No. 11 Clemson 33-21 in 2024, and did it again last season with a 24-21 road win over No. 2 Miami. The Cardinals entered all three games as underdogs, just as they will Sunday night against Ole Miss.
And this goes back well before Brohm returned to Louisville. At Purdue, his teams pulled off a 49-20 win over No. 2 Ohio State in 2018, then knocked off No. 2 Iowa 24-7 and No. 3 Michigan State 40-29 during the 2021 season.
So, Ole Miss certainly shouldn’t overlook this Louisville team. Brohm will once again try to draw up a game plan capable of taking down a top-10 opponent, and he has some serious talent to work with. Running back Isaac Brown is back after averaging an absurd 8.8 yards per carry last season and remains a threat to take one to the house every time he touches the ball.
On the other side, defensive lineman Clev Lubin returns after recording 8.5 sacks and three forced fumbles in 2025. Brown and Lubin were also Louisville’s two selections to the 2026 Preseason All-ACC Team, giving the Cardinals a difference-maker on each side of the ball.
Brohm has pulled off this type of upset plenty of times before. Now we’ll see if he has another one up his sleeve against No. 9 Ole Miss.
Perhaps the biggest storyline surrounding Ole Miss this season is pretty obvious: life without Lane Kiffin. Pete Golding took over during last year’s College Football Playoff run and immediately led the Rebels to wins over Tulane and SEC rival Georgia before coming up just short against Miami in the semifinals.
Coming off that run, expectations are still sky-high in Oxford. The question now is whether Golding can pick up where Kiffin left off over the course of a full season.
There are certainly some question marks. John David Baker takes over as offensive coordinator after Charlie Weis Jr. followed Kiffin to LSU, and the Rebels must replace five of their top six pass-catchers from last season. That puts plenty of pressure on newcomers like Johntay Cook II and Horatio Fields to quickly develop chemistry with Trinidad Chambliss.
There are some concerns up front as well. Ole Miss lost both starting tackles to the NFL and will rely on a mix of transfers and less-proven options to protect Chambliss. The defense has plenty of talent, but it also lost seven starters from last year’s group, leaving Golding with quite a bit to replace on both sides of the ball.
And there won’t be much room for growing pains. After opening against a ranked Louisville team, Ole Miss still has LSU, Georgia, Missouri, Texas, and Oklahoma waiting later on the schedule. If the Rebels want to make another run at the College Football Playoff, Golding and his new-look staff will have to get things figured out pretty quickly.
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