Notre Dame vs. Louisville Predictions, Picks & Odds Week 6: Can Fighting Irish Earn Another Road Win?

Check out our Notre Dame vs. Louisville prediction for their Week 6 college football matchup based on the best NCAAF odds.

Brenden Schaeffer

Last Updated: October 7, 2023 2:14 PM EDT • 4 minute read

The Notre Dame Fighting Irish embark on a road trip to face the Louisville Cardinals, and we provide our expert prediction for the Notre Dame vs. Louisville matchup, considering the Irish's track record on away games. Dive into our in-depth analysis, factoring in the college football odds gathered from the best sports betting apps.

A visit to the Bluegrass State is unlikely to hinder the CFP National Championship aspirations of the 5-1 Notre Dame Fighting Irish this Saturday. Having defeated two ACC opponents on the road already this season, they enter the matchup as hefty favorites against the unbeaten 5-0 Louisville Cardinals.

Here is our best Notre Dame vs. Louisville prediction and our college football picks (odds via our best college football betting sites; pick confidence based on a 1-to-5-star scale).

Notre Dame vs. Louisville prediction

Notre Dame -6 (-110 via DraftKings) ⭐⭐⭐⭐

Notre Dame just did this a week ago, going on the road to a quality ACC opponent and winning the game by a touchdown at Duke.

I actually think Duke was the tougher matchup for the Irish than this upcoming affair at Louisville, as Duke ranks virtually identically to Louisville in adjusted offensive efficiency, but falls 18 spots lower in defensive efficiency, checking in at No. 31 in the nation.

Sam Hartman and the Fighting Irish were bottled up somewhat offensively in that matchup at Duke, scoring just 21 points and needing a late touchdown to ensure the victory. That’s not been the norm for this explosive passing game, and Louisville ranks 86th in the FBS in pass defense, allowing 254.8 yards per game through the air. That’s a more forgiving unit than Duke’s top-20 pass defense that Notre Dame just faced.

Notre Dame has a top-10 offense to pair with a top-25 defense in terms of adjusted efficiency. It’s a CFP-caliber roster that needs to run the table to remain in consideration for an opportunity.

Notre Dame is 4-1-1 against the spread this season, while Louisville has gone just 2-3 ATS. The motivation should be here for the Irish to win another tough road contest by a touchdown.

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Notre Dame vs. Louisville best odds

Notre Dame -6 (-110)

DraftKings	FanDuel	BetMGM	Caesars	bet365
Notre Dame -6	ND -6.5	ND -6.5	ND -6.5	ND -6.5
-110	-110	-110	-110	-110

DraftKings is the obvious choice to bet the Irish on the spread, as it's the only sportsbook to offer -6 instead of -6.5.

At -6, this is a four-star recommendation. If DraftKings’ island line ends up disappearing, we’re still playing Notre Dame at -6.5, but as a three-star play.

Notre Dame vs. Louisville odds

Notre Dame vs. Louisville odds analysis

Notre Dame opened as a 6.5-point favorite and has remained at that number across our affiliated sportsbooks with the exception of DraftKings, which has moved the line to -6. The Irish are seeing 61% of spread bets.

The total opened at 56.5 and is currently floating between 53.5 and 54 across our recommended sportsbooks. Most bettors are attacking the new line, as 68% of wagers have gone Over.

Notre Dame vs. Louisville game info

When: Saturday, Oct. 7 at 7:30 p.m. ET
Where: L&N Federal Credit Union Stadium, Louisville, KY
How to watch: ABC
Weather: 55 degrees, 13 mph winds, 0% precipitation

Notre Dame-Louisville prediction made 10/05/2023 at 3 p.m. ET.

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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 NFL player prop markets 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.