Louisville vs Ole Miss: Preview and Predictions

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Louisville vs. Ole Miss — | Source: Lastwordonsports.com – Tony Siracusa, CFB Managing Editor

After eight long months, we’ve finally made it. Week one kicks off this weekend, which provides us with the first full slate of games for the 2026 college football season. And while this year’s week one may not have quite the same caliber of games that we’ve seen in seasons past, there are still plenty of intriguing games to keep an eye on. Louisville vs Ole Miss is one of those matchups, as it’s the only game between two ranked opponents during the weekend.

It’s also a neutral site game, taking place in Nashville, so neither team should have much of a home field advantage.

With that being said, who has the advantage on the field in this one, and can the Cardinals ultimately pull off the upset in the season opener?

Previewing Louisville vs Ole Miss

Keys for Louisville to Pull Off the Upset

There are a few guarantees when it comes to college football. One of those guarantees is that Louisville head coach Jeff Brohm is always going to have his teams play physical, disciplined football. This is one of the biggest reasons he’s led the Cardinals to nine or more wins in each of his three seasons at the helm. And there’s no real reason to think that is going to change in 2026.

But in this matchup, the biggest key for Louisville is the defense. In 2025, they finished the country ranked 16th in total defense. Now, they open this season taking on a school that is well known for having elite offenses and brings back two potential Heisman candidates. Needless to say, the Cardinals are going to have to limit the number of explosive plays they give up to this Ole Miss offense. If they can shorten the Rebels’ drives on the offensive side of the ball, and potentially come up with a turnover or two along the way, they’re going to find themselves in really good shape to pull off the upset late in the fourth quarter.

On the offensive side, expect to see a heavy dose of running back Isaac Brown. During the 2025 season, he averaged 8.8 yards per carry, rushing for 884 yards on just 101 carries. Against what is expected to be a good Rebel defensive line, he’s going to have to continue to find similar success. But that also falls on the backs of the Cardinals’ offensive line. Can they get enough push off the ball to allow Brown to have a big day?

If there is one question for Louisville, it comes at quarterback. Ohio State transfer Lincoln Kienholz will be taking snaps for Brohm’s offense, in what will be the first start of his career. Last season, as a backup, he completed 11 of his 14 passes for 139 yards and a touchdown. He also added 11 rushes for 66 yards and two scores. He’s known as a dual-threat guy, and the numbers back that up.

However, the question is with his lack of experience. Taking on a Rebel defense that is going to be physical and try to get into the backfield on every play is sure to be a tough test for a player making his first start of his career.

How Do the Rebels Leave Nashville With a Win?

Defense.

Taking on a team with a quarterback making his first start, the Rebel defense is going to have to have a big day. They struggled a bit last season, but added a ton of talent and depth to the roster during the offseason. If guys like Will Echoles and Suntarine Perkins can get into the backfield consistently, it will keep Kienholz from finding a rhythm and feel for the game. That would allow them to largely turn the Cardinals into a one-dimensional offense, which is going to be the biggest key for Ole Miss to have success on that side of the football.

On the offensive side of the ball, the only big question is what kind of scheme new offensive coordinator John David Baker decides to draw up. We know about the talent of Trinidad Chambliss and Kewan Lacy in the backfield. The offensive line is returning three starters and brought in talent through the portal. On the outside, while they lost a lot of production at the receiver position, they also replaced it with a ton of guys; it just becomes a question of which player is going to step up.

The big question is the new system. But with Baker having already been in Oxford for a previous stint, most people expect and understand that the offense won’t change all that much from what it looked like under Lane Kiffin and Charlie Weis Jr. So even with a new play caller, the Rebel offense should still look similar to what Ole Miss fans have grown accustomed to seeing.

Louisville vs Ole Miss Predictions

This is a game that should largely come down to the trenches. We know both running backs are elite. There are questions for both teams at receiver. So which offensive line can hold up for the quarterback better? If the Rebel offensive line can hold up for Chambliss, we’ve seen that he can make explosive plays. For Louisville, there are still a lot of questions about Kienholz.

And then there’s the defense. Ole Miss likely has more talent and depth in their front seven than the Cardinals. Against a questionable Louisville offensive line, and with a new quarterback, that should be a huge advantage for the Rebels.

We all know that Brohm-led teams are well coached and disciplined. We also know that we only have an extremely small sample size when it comes to Ole Miss head coach Pete Golding. That being said, don’t expect this game to be a blowout going either direction. It’s going to be a good game that should be close well into the second half.

But in the end, expect experience to ultimately win out. The Rebels force a turnover late to sneak away with a big season-opening win.

Ole Miss 31, Louisville 20

How to Watch Louisville vs Ole Miss

Date: Sunday, September 6; Time: 7:30 ET

Location: Nissan Stadium

TV: ABC

Main Image: Nathan Ray Seebeck-Imagn Images