Ole Miss vs. Louisville Predictions: Who Wins and Why?

No. 9 Ole Miss kicks off its 2026 season in Nashville against No. 24 Louisville on Sunday. The showdown at Nissan Stadium will be the first nationally ranked matchup of the college football season.

The ninth-ranked Rebels are seeking to pick up right where they left off last season, beating some of the top teams on their way to reaching the national semifinal. Though Sunday will mark Pete Golding’s first regular season game of his head coaching career, Ole Miss got a glimpse of what its new era could be like as the Rebels went 2-1 through their run in the College Football Playoffs.

Louisville is no slouch either, believing it also has a team worthy of potentially qualifying for the CFP by December. Head coach Jeff Brohm has led the Cardinals to at least nine wins in each of the last three seasons. Louisville went 9-3 through its regular season last fall, including an upset victory over, then, No. 2 Miami — who Ole Miss went on to lose to in the Fiesta Bowl.

Ahead of the anticipated Week 1 matchup, the Ole Miss On SI staff makes its game picks between the Rebels and Cardinals. Kickoff is set for 6:30 p.m. CT on ABC.

Louisville Cardinals running back Isaac Brown (1) scores a big fourth quarter touchdown against James Madison. — Louisville Cardinals running back Isaac Brown (1) scores a big fourth quarter touchdown against James Madison during the Cards' second college football game Friday September 5, 2025 at L&N Credit Union Stadium in Louisville, Kentucky. The Cards beat the Dukes 28-14. | USA TODAY Network via Reuters Connect

Tyler Komis (Record: 0-0)

Entering Sunday’s matchup, I have questions for both teams. However, there are far more questions surrounding the Cardinals than the Rebels.

Louisville is replacing four of its five starting offensive linemen from a season ago. How is that going to look? We’ll see soon enough, but the unit’s first challenge comes against a touted Ole Miss defensive line that, internally, has drawn comparisons to the dominant one it trotted out in 2024. That’s already a favorable, and critical, matchup for the Rebels. Behind that offensive line is first-year starter Lincoln Kienholz, who will need a reliable run game to lean on in order to keep up. Isaac Brown could be one of the best players on the field, but should Ole Miss limit the Cardinals’ star running back and force a one-dimensional attack, the Rebels win comfortably.

Though Louisville is capable of pulling off the upset, most factors favor the Rebels. Regardless, I think Ole Miss gets a nice opening-weekend test in Music City.

Ole Miss 31, Louisville 21

Daylan Flowers (Record: 0-0)

Ole Miss comes into the season with heavy expectations, after a berth in the CFP last season, a great production of returning and new talent hopes to lead the Rebels back to the postseason. Jeff Brohm is a respected coach, a Cardinals team that won 9 games last season, had some changes, but will be an early test for first year head coach Pete Golding. This game will be won in the trenches, which favors the Rebels. Ole Miss must take care of the football, create big plays early, and execute in the redzone, and if they do all these things, they will start the season 1-0.

Ole Miss 31, Louisville 17

Jaydon Koss (Record: 0-0)

My score prediction makes the game look a lot closer than how I expect it to play out. I see Pete Golding’s defense causing a rocky start for Louisville quarterback Lincoln Kienholz, leaving most of the heavy lifting to be done by running back Issac Brown. The problem for Louisville, though, is that as good as Brown is, Ole Miss running back Kewan Lacy might be better. A strong running game and defensive performance would likely be enough for Ole Miss to go up early, possibly forcing Louisville to put the game on the arm of Kienholz. If it comes down to a duel between the quarterbacks, there is no doubt I have more faith in Ole Miss’ Trinidad Chambliss to come out on top.

Ole Miss 27, Louisville 17

Zion Trammell (Record: 0-0)

Saturday’s game features star running backs with Kewan Lacy and Isaac Brown. We could see a run-heavy scheme from both sides, but Ole Miss has the offensive advantage. Chambliss and Lacy will be the difference-makers in this game, and the Rebels will get a massive season-opening victory.

Ole Miss 31, Louisville 24

Tanner Shapiro (Record: 0-0)

The Rebels head into Nashville with the goal of making the playoffs once again after reaching the College Football Playoff in 2025. Ole Miss opens the season against the No. 24 Louisville Cardinals, but the return of Trinidad Chambliss and another season with Kewan Lacy in the backfield should prove to be too much for Louisville in Week 1. The linebacker duo of Luke Ferrelli and Keaton Thomas should be able to slow down Louisville running back Isaac Brown just enough for the Rebels to escape Week 1 with a win.

Ole Miss 31, Louisville 20

Ethan Tavel (Record: 0-0)

There is a big talent gap in this matchup, with quarterback Trinidad Chambliss and running back Kewan Lacy. Chambliss led the SEC in passing yards with 3,937 and finished eighth in Heisman voting, and Lacy rushed for a program-best 24 touchdowns and was named a unanimous preseason All-American. Ole Miss has two proven stars that the Cardinals will have trouble game-planning for.

While the Cardinals can definitely keep it close on Sunday, the Rebels have the firepower to pull out a win in Nashville, and will do just that.

Ole Miss 31, Louisville 17

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