Louisville vs. Syracuse Prediction, Odds, Spread and Over/Under for College Football Week 1

The Louisville Cardinals have three straight blowout wins over the Syracuse Orange, with the last two coming by a combined score of 71-3. Led by All-American running back Sean Tucker, the Orange hope for better results in Week 1 this year.

Syracuse should take a step forward offensively after an assistant coach overhaul. After scoring only 34 points in its last three games combined though, their offense has a lot of improvement to make.

Perhaps the Cardinals could lend some offensive firepower to their foes, because good grief, this offense is electric. Four starters return on the offensive line to support quarterback Malik Cunningham, one of the most dangerous players in the sport. He threw for four touchdowns and ran for another against 'Cuse last year and should only improve in his final collegiate campaign.

Will Louisville secure another blowout or can the Orange pull off the upset? Here are the odds from WynnBET Sportsbook before we dive into it:

Louisville vs Syracuse Odds, Spread and Total

Louisville vs Syracuse Betting Trends

Louisville

• 3-0 against the spread (ATS) last three games against Syracuse

• OVER is 3-1 last four games

• 3-1 ATS last four games as road favorites

Syracuse

• 10-4 ATS last 14 games

• UNDER is 6-2 last eight games as home underdogs

• 1-9 outright last 10 games as home underdogs

Louisville vs Syracuse Prediction and Pick

Sean Tucker compiled 1,751 yards from scrimmage last season and 14 touchdowns for Syracuse while quarterback Garrett Shrader added 781 rushing yards with 14 scores of his own, but I don't think even those two can keep up with Malik Cunningham.

The latest stud dual-threat signal caller for the Cardinals threw for a career-high 2,941 yards in 2021 while rushing for over 1,000 yards with 39 total touchdowns. This should be the best offensive line Cunningham ever played behind, and he could be in for a Heisman-type season.

Syracuse's defensive front won't be able to contain Cunningham, and its offensive isn't explosive enough to keep up. With a spread of only four points, I love the value on Louisville to open 2022 with a bang.

Back the Cardinals to improve to 11-5 in their last 16 games as favorites thanks to an overwhelming offensive onslaught.

PICK: Louisville -4 (-110)

Follow all of Joe Summers' betting picks here.

Need Week 1 picks? Catch all of The Early Reed's Week 1 bets!