Wake Forest vs. Louisville Prediction, Odds and Key Players to Watch for College Football Week 4

Louisville is favored against Wake Forest in Week 4 of the college football season. | IMAGN IMAGES via Reuters Connect

The Louisville Cardinals started their 2026 ACC schedule with a significant 41-31 win against the SMU Mustangs. They'll look to keep their momentum going when they take on the Wake Forest Demon Deacons in Week 4.

Wake Forest had the tough challenge of facing the best team in the conference in its first ACC game, falling to the Miami Hurricanes 33-20. If they want to establish themselves as a legitimate team in this conference, they can do so by upsetting the Cardinals on Saturday.

Let's dive into the odds and my best bet for this ACC game.

Wake Forest vs. Louisville Odds, Spread, and Total

Odds via Caesars Sportsbook

Spread

• Wake Forest +12.5 (-108)
• Louisville -12.5 (-112)

Moneyline

• Wake Forest +390
• Louisville -530

Total

• OVER 58.5 (-113)
• UNDER 58.5 (-107)

Wake Forest vs. Louisville How to Watch

• Date: Saturday, September 26
• Time: Noon ET
• Venue: L&N Federal Credit Union Stadium
• How to Watch (TV): ESPN/Disney+
• Wake Forest record: 2-1
• Louisville record: 2-1

Wake Forest vs. Louisville Betting Trends

• The OVER is 6-4 in the last 10 meetings between these two teams
• Wake Forest is 6-4 against the spread in its last 10 games
• The OVER is 6-4 in Wake Forest's last 10 games
• The OVER is 6-4 in Louisville's last 10 games

Wake Forest vs. Louisville Key Player to Watch

• Keyjuan Brown, RB - Louisville Cardinals

Isaac Brown is the No. 1 running back for this team, but he's struggled to begin the season, rushing for just 164 yards and 4.2 yards per carry. By comparison, Keyjuan Brown has rushed for 231 yards on 21 fewer carries, averaging a blistering 12.8 yards per rush. If those numbers continue, the Cardinals will have no choice but to start giving Keyjuan more carries.

Wake Forest vs. Louisville Prediction and Best Bet

I don't think the betting market has quite caught up to how good this Louisville team is. Despite having a relatively tough schedule to begin the season, the Cardinals have averaged 7.0 yards per snap, the 13th-best mark in the nation.

That's bad news for the Demon Deacons, whose defense ranks 49th in opponent yards per play, giving up 5.1 yards per snap.

Don't overrate Wake Forest just because they covered against Miami last week. The Hurricanes stumbled in a big way in the second half of that game.

I'm going to lay the points with Louisville in this spot.

Pick: Louisville -12.5 (-112) via Caesars Sportsbook

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