Wake Forest vs. Louisville Prediction, Betting Pick, Latest CFB Odds for Saturday, September 26th
The Wake Forest Demon Deacons head back on the road for an ACC matchup against No. 16 Louisville after hanging around with Miami deep into the fourth quarter. Can Gio Lopez and the Demon Deacons create enough explosive offense to stay within two touchdowns against a Cardinals team coming off a ranked victory over SMU? Check out this Wake Forest vs. Louisville prediction and best bet for Saturday, September 26.
Peter Alexis - September 26, 2026, 9:00 AM EDT
5 Minute ReadWake Forest vs. Louisville Prediction: Can Wake Play Close with Lincoln Keinholz, Red-Hot Cardinals on Saturday?
Wake Forest enters at 2-1 and 0-1 in ACC play after a 33-20 loss to Miami, while Louisville is 2-1 and 1-0 after beating SMU 41-31. Kickoff is scheduled for noon ET on ESPN at L&N Federal Credit Union Stadium.
Louisville deserves to be favored at home, but the market is asking the Cardinals to clear 12.5 points against a Wake team that has already won at Purdue and stayed competitive against one of the country's best teams.
Wake Forest vs. Louisville Recent Results
Wake Forest Demon Deacons (2-1), (0-1 ACC)
Wake Forest suffered its first loss Friday night, falling 33-20 to Miami. The Demon Deacons stayed competitive despite facing an offense that entered the game in elite form, and the final margin still landed inside two touchdowns.
That came after Wake won 38-36 in double overtime at Purdue, giving Jake Dickert's team two early examples of handling difficult game scripts. Lopez's mobility remains the centerpiece of an offense that has already shown it can score against Power Four competition.
Louisville Cardinals (2-1), (1-0 ACC)
Louisville opened conference play with a 41-31 win over ranked SMU, bouncing back from its season-opening loss to Ole Miss. The Cardinals created enough defensive disruption to slow one of the ACC's most explosive passing offenses while continuing to produce on the ground.
Louisville has now demonstrated that it can score into the 40s against quality competition. The issue for this spread is that its defense has also allowed opponents to generate enough offense to keep games competitive.
Wake Forest vs. Louisville Head to Head
Louisville leads the all-time series 7-3 and has won the most recent meeting.
- October 29, 2022: Louisville 48, Wake Forest 21
- October 2, 2021: Wake Forest 37, Louisville 34
- December 12, 2020: Louisville 45, Wake Forest 21
- October 12, 2019: Louisville 62, Wake Forest 59
This series has produced several high-scoring games, and Wake has won in Louisville before, taking a 56-35 decision in 2018. The 2022 blowout is the cautionary example, but the current Wake offense has more quarterback mobility than that final margin suggests.
Wake Forest vs. Louisville Date, Time, Where to Watch
- Date: Saturday, September 26th, 2026
- Time: 12:00 PM ET
- Location: L&N Federal Credit Union Stadium, Louisville, KY
- How to Watch: ESPN
Wake Forest vs. Louisville Odds
- Spread: Wake Forest +12.5 (-110), Louisville -12.5 (-110)
- Total Points: Over 58.5 (-110), Under 58.5 (-110)
- Moneyline: Wake Forest (+390), Louisville (-520)
Click here for the latest Wake Forest vs. Louisville Odds
Wake Forest vs. Louisville Line Movement and Betting Splits
The spread has remained near Louisville -12.5, but the betting split is dramatically different depending on whether tickets or money are considered. Roughly three-quarters of DraftKings spread bets are on Louisville, while around 60% to 70% of the handle has been landing on Wake Forest.
The Over has drawn essentially all tracked total action. That reinforces expectations for a high-scoring game, which naturally creates more opportunities for the underdog to stay inside a large spread.
Wake Forest vs. Louisville Prediction
Louisville has the offensive ceiling to create separation. The Cardinals just scored 41 against SMU and have already shown they can produce explosive plays against ranked competition.
Wake's best weapon against that is Lopez. A mobile quarterback gives an underdog multiple ways to extend possessions when protection breaks down, and Lopez has already shown he can keep the offense alive on third down with both his arm and legs.
The Demon Deacons also have experience playing from behind. They fell behind Purdue and still won in overtime, then stayed close enough with Miami that the Hurricanes could not fully put the game away until late. That resilience matters with nearly two touchdowns in hand.
Louisville's defense is disruptive but not impenetrable. Ole Miss scored 41 in the opener, and SMU reached 31 last week. Wake does not need to match Louisville score for score, but reaching the mid-20s makes -12.5 significantly harder for the favorite to clear.
The betting split is also unusually supportive of the underdog. Louisville is getting the majority of individual bets, yet the larger average wager is landing on Wake Forest. That does not guarantee the result, but it fits a number that may be slightly too large.
The biggest concern is Louisville's ability to turn turnovers into immediate separation. Wake cannot give the Cardinals short fields and expect to survive. Lopez needs to play aggressively enough to score without forcing throws into pressure.
Wake Forest vs. Louisville Best Bet
- Best Bet: Wake Forest +12.5 (-110) Check out these best odds at DraftKings Sportsbook
Louisville deserves to be favored and should have the stronger offense, but Wake has already shown it can compete in difficult road environments and against ranked competition. Lopez gives the Demon Deacons enough playmaking to keep Louisville from comfortably controlling every possession.
With most tickets on Louisville but the majority of DraftKings spread money landing on Wake, the underdog has both a matchup path and a favorable market profile. A 34-27 or 38-28 Louisville win keeps Wake inside the number.
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