Louisville football enters the 2025 season with the third-best odds to win the ACC Championship at +850, trailing only Clemson (+115) and Miami (+440). Coming off a year where they lost just three conference games — all by a touchdown or less — the Cardinals appear poised for another run at the ACC title under head coach Jeff Brohm.
While marquee matchups against Clemson (at home) and Miami (on the road) stand out, the season’s true tipping points may come elsewhere on the schedule.
Last season, despite beating Clemson, Louisville fell two games short of the ACC Championship due to a November collapse at Stanford and a high-scoring home loss to Miami. In college football, it's often the unexpected slip-ups — not just the headline games — that define a season.
The 2025 slate is no cakewalk, but it sets up favorably enough for the Cardinals to make another ACC title push.
3 must-win games that will make or break Louisville’s 2025 season
3. At Virginia Tech – Nov. 1
Louisville is 0–3 all-time on the road against the Hokies, and Blacksburg remains one of the tougher environments in the ACC. Virginia Tech is expected to be a middle-of-the-pack team with a projected win total of 6.5 — just good enough to be dangerous.
This is exactly the kind of game Louisville has struggled with in the Brohm era (think: at Pitt in 2023, at Stanford in 2024). A win here, sandwiched between matchups with Miami and Clemson, would show growth and could be critical to staying on pace in the ACC race.
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2. At Pittsburgh – Sept. 27
Pitt has been a consistent thorn in Louisville’s side. Since joining the ACC, the Cardinals are just 2–3 against the Panthers and 5–8 all-time on the road in the series. While the Panthers' season was a disaster, they still showed they can be a spoiler team in the ACC, and the Cardinals are getting them as their first ACC opponent in week 5.
The Panthers are going to be challenging, and last year they proved they can be a contender early in the season. The Cardinals blew them out last year, 37-9, but now with this game on the road and early in the season, Brohm's Cardinals will have a much bigger challenge.
This is Louisville’s first real test of the season, and don't be surprised if this game comes down to the fourth quarter. A win could set the tone for an ACC title run — while a loss might force the Cards to play catch-up the rest of the way. Louisville will be coming off three relatively cakewalk opponents, all from L&N Stadium, so with this being their first road test and first ACC matchup, it will be crucial for Louisville to walk away with a win.
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1. At SMU – Nov. 22
This could be the biggest trap game of the year — or the most important resume booster.
SMU brings back much of the roster that earned them an at-large College Football Playoff bid last season, including breakout quarterback Kevin Jennings. The Mustangs are legitimate contenders, and their high-octane offense will test Louisville’s defense late in the year.
What makes this game even more dangerous: it falls between two emotional rivalry games — Clemson the week before and Kentucky the week after. If Louisville is in contention for the ACC title or a playoff spot, they’ll need to prove they can handle business in a tough road environment against a battle-tested opponent.