This article is part of our College Football Picks series.
Notre Dame 
@ Ohio State Betting Odds, Picks, and Predictions for Week 1
Saturday's game will mark the first meeting between these two historic powerhouse programs since 1996, though introductions are likely unnecessary. First-year head coach Marcus Freeman has the Fighting Irish faithful optimistic about the trajectory of the program for years to come, but he immediately faces a massive Week 1 test against his alma mater led by preseason Heisman favorite C.J. Stroud. The Buckeyes have no shortage of returning firepower from last year's top-ranked offense, leaving Notre Dame as significant underdogs in this marquee matchup of preseason top-5 ranked teams.
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Notre Dame @ Ohio State Odds for Week 1
Spread: Notre Dame +17.5 (Caesars Sportsbook)
Total: 59 (Caesars Sportsbook)
Moneyline: Notre Dame +550; Ohio State -800 (Caesars Sportsbook)
The opening line already had Ohio State favored by more than two scores (-14.5) and the Buckeyes have since gained an additional field-goal advantage. While this movement isn't surprising given the general public's annual dismissal of Notre Dame as an overrated program, it also speaks to the understandable widely-held confidence in the Buckeyes' offensive potential.
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Notre Dame @ Ohio State Betting Picks This Week
It's hard to imagine that Ryan Day's offense, which ranked first nationally in efficiency (45.3%), yards per play (8.1), scoring (45.7 ppg) and total yards (561.5 ypg) last year, won't roll with playmakers like wideout Jaxon Smith-Njigba and running back TreVeyon Henderson back for more in 2021. Slowing down this bevy of offensive firepower seems too tall a task for even Notre Dame's impressive core of starting defenders. Though, the odds that the Buckeyes will completely snuff out the Fighting Irish's offense seem similarly unlikely given that this unit ranked 21st in SP+ and averaged 35.2 points per game just last year. This would be right in line with the 2021 betting trends for Ohio State, with an average final combined total of 68.5 points and eight out of 13 combined overs hit last year.
Notre Dame vs. Ohio State Best Bet: OVER 59 at Caesars Sportsbook
Notre Dame @ Ohio State Prediction
Both Notre Dame and Ohio State brought in new, well-respected defensive coordinators this offseason in Al Golden and Jim Knowles, respectively, so it could take some time for both units to get settled in. Don't be surprised if this causes Knowles' unit (designed to confuse opposing offenses and create havoc) to give up one or two explosive plays to dual-threat quarterback Tyler Buchner. Still, I wouldn't expect a true track-meet-style game as Notre Dame's offense isn't built to move all that fast. The Fighting Irish do have multiple high-level starting players on defense, but it shouldn't take long before Ohio State's immensely talented corps of wideouts eventually exposes a lack of proven depth in their opponents' secondary. In the end, there should be enough back-and-forth scoring to push up the total while maintaining a respectable margin of defeat (and maybe even a sneaky backdoor cover) for the nation's fifth-ranked team.
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