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Wake Forest vs. Louisville Prediction: Week 4 Odds, Picks & Best Bet

Our Wake Forest vs. Louisville prediction for Week 4 includes our best bet, projected score, and the latest odds for Saturday's matchup.

Brenden Schaeffer

Last Updated: September 25, 2026 3:05 PM EDT • 2 minute read

Pictured: Louisville quarterback Lincoln Kienholz (3) looks on as we break down our Wake Forest vs. Louisville prediction. Photo by Chris Carter-Imagn Images.

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My Wake Forest vs. Louisville prediction anticipates a standout effort from both offenses Saturday, as each side will be opposed by a less-efficient unit on the other side. No. 16 Louisville’s aspirations hinge on a quarterback who is proving himself weekly.

Louisville is a 13.5-point betting favorite, with kickoff from L&N Federal Credit Union Stadium in Louisville, Ky., set for noon ET (ESPN, Disney+).

🏈 Wake Forest vs. Louisville picks & predictions

See all of our experts' college football picks for Week 4 based on the latest college football odds.

Pick	Bet size
ATS: Wake Forest +13.5 (-110 via FanDuel)	0.5 units
O/U: Over 56.5 (-115 via DraftKings)	1.0 units

Total wagered: 1.5 units | Max profit: +1.26 units

💰 Wake Forest vs. Louisville prediction & best bet

Check out all of our college football predictions for more analysis across this week's slate.

Over 56.5 (-115 via DraftKings)

An element of the Louisville football team about which I came into the season with sincere skepticism but have had to change my tune regarding has been my expectations for Lincoln Kienholz. The Ohio State transfer has the juice.

He’s taken care of the football through three weeks, sporting a 6-0 TD-INT ratio and has added strong rushing outputs, as well. So, I expect Kienholz to put up points on a Wake Forest defense that ranks 93rd in FPI’s adjusted defensive efficiency. In two Power Four games, the Deacons have allowed 33 points to Miami and 23 in regulation to Purdue (36 including OT).

Both teams rank far more favorably in adjusted offensive efficiency than they do on the defensive side, which could lead to a friendly environment for points.

This line has actually come down since opening at 58.5, which works to our favor on this play. We’re playing Over 56.5 at DraftKings, though I wouldn’t shy from the 57.5 number at FanDuel and would be willing to play this Over up to 59.5 points.

📡 SBR EDGE

Louisville’s defense has allowed 36.0 PPG across its two FBS matchups this season.

Mobile QB could be a problem for Wake

Wake Forest didn’t face a mobile quarterback in either of its Power Four games, but its performance defensively against Akron’s Cibastian Broughton could be cause for concern against the athletic Kienholz.

Broughton torched the Wake defense for 5.9 YPC, racking up 82 rushing yards on 14 rushing attempts, which could lend toward what we might see from Kienholz on the ground this week.

Score prediction: Louisville 38, Wake Forest 27

📊 Wake Forest vs. Louisville odds

See the latest college football odds for every Week 4 matchup.

Wake Forest vs. Louisville opening odds

Moneyline: Wake Forest +400 | Louisville -525
Spread: Wake Forest +13 (-110) | Louisville -13 (-110)
Over/Under: Over 58.5 (-110) | Under 58.5 (-110)

📺 How to watch Wake Forest vs. Louisville: Week 4

Date: Saturday, Sept. 26
Kickoff: Noon. ET
Location: L&N Federal Credit Union Stadium (Louisville, Ky.)
TV: ESPN
Streaming: Disney+

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Written by:
Brenden Schaeffer

Brenden has covered the St. Louis Cardinals as a credentialed baseball writer for KMOV-TV since 2016. His sports writing has appeared in outlets including the Austin American-Statesman and Columbia Daily Tribune. Since 2021, Brenden has co-hosted 'The Big Show' during the afternoon drive for KTGR, the ESPN radio affiliate in Columbia, MO. He has appeared on radio stations around the country, including KMOX, and hosts a daily St. Louis Cardinals podcast. In the sports betting content space, Brenden has covered the NFL, college football, NBA, and college basketball for outlets including SBR since 2019. For his football handicapping, Brenden looks to target player prop markets using his NFL experience, as well as sharp underdog lines in college football. Brenden looks to reference FanDuel for his sports betting articles because of its consistently competitive odds on parlays. FanDuel's boost offerings are also customer-friendly, and its odds on the NFL Same Game Parlay articles he's written for SBR have historically been consistently competitive compared to other books.