Florida State vs. Louisville Prediction, Odds and Key Players to Watch for College Football Week 6

An interesting ACC matchup is set for Friday night in Week 6, as the Florida State Seminoles (3-2) take on a once-ranked Louisville Cardinals squad that has dropped back-to-back games.

Louisville is just 2-3 this season with three losses against Power 4 programs, including back-to-back defeats in ACC play by three points (against Wake Forest and NC State).

Despite that, oddsmakers have Louisville favored at home against the Seminoles and quarterback Ashton Daniels.

Florida State has one of the best run games in the country, and it held its own earlier this season in a loss to a top-10 team in Alabama. Both of these teams have a common opponent in 2026 in SMU, which beat Florida State but lost to Louisville by 10 points.

Can the Cardinals get back on track with a key conference win?

Let’s take a look at the odds, a player to watch and my prediction for Friday’s battle.

Florida State vs. Louisville Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

Florida State +4 (-108)
Louisville -4 (-112)

Moneyline

Florida State: +164
Louisville: -198

Total

59.5 (Over -105/Under -115)

Florida State vs. Louisville How to Watch

Date: Friday, Oct. 9
Time: 7:00 p.m. EST
Venue: L&N Federal Credit Union Stadium
How to Watch (TV): ESPN
Florida State record: 3-2
Louisville record: 2-3

Florida State vs. Louisville Key Player to Watch

Ashton Daniels, Quarterback, Florida State

This season, Daniels has completed 60.3 percent of his passes for the Seminoles for 1,111 yards, six touchdowns and six interceptions, making him one of the more volatile passers in the country.

Florida State ranks 51st in the country in EPA/Pass, but it has been great on the ground (12th in EPA/Rush), where Daniels has also made a massive impact.

The dual-threat quarterback has 57 carries for 278 yards and nine touchdowns, leading the team in rushing (136 yards) in last week’s blowout win over Virginia.

The Louisville defense is just 116th in the country in EPA/Pass this season, so Daniels and the Seminoles may be able to attack through the air on Friday night.

Florida State vs. Louisville Prediction and Pick

Both of Florida State’s losses have come to ranked opponents this season, losing by three against SMU and by 14 against Alabama. However, it picked up a huge win over Virginia in Week 5, and it may be undervalued as an underdog on a short week.

Louisville has struggled against other Power 4 teams through five games, dropping games against Ole Miss, Wake Forest and NC State, though it did beat SMU by 10 points.

The Cardinals are 23rd in the country in net adjusted EPA/Play (better than Florida State at 36th), but the Seminoles are the No. 8 offense so far this season.

That could be a problem for a Louisville team that has allowed at least 27 points in every single game against a Power Four team in 2026.

Both of these teams rank outside the top 70 in defensive success rate in 2026, and they’re both 100th or worse in EPA/Pass.

Still, I like the Seminoles in this matchup since they can control the game on the ground (12th in EPA/Rush) and are tied for 13th in third/fourth down success rate. Florida State getting more than a field goal is a gift against a Louisville team that is under .500 in 2026.

Pick: Florida State +4 (-108 at DraftKings)

Odds refresh periodically and are subject to change.

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