Syracuse Orange vs Notre Dame Fighting Irish Prediction, Odds and Picks for Tomorrow, 11/22/25

It will be Senior Day in South Bend when the Notre Dame Fighting Irish host the Syracuse Orange on Saturday. The Irish have won 8 straight after losing to Miami and Texas A&M by 4 combined points in consecutive weeks at the beginning of the season, and the College Football Playoff committee feels that they have done enough to warrant a spot in the 12-team postseason. Meanwhile, Syracuse is almost in the exact opposite position as Notre Dame. The Orange are 3-7 SU and are losers of 6 in a row – including their most recent 38-10 defeat against Miami prior to their bye week. During this 6-game skid, the Orange have failed to surpass 20 points even once. In fact, ‘Cuse has failed to reach 17 points in each of its last 4. 

Notre Dame is no stranger to being a 3+ touchdown favorite; the Irish have been at least -21 5 times this year and are 3-1-1 ATS in those games. This includes 2 games in which the Irish were laying exactly 31 points. As for Syracuse, the Orange have only been a 20+ point underdog once this year, which was last game when they barely snuck in as 28.5-point underdogs in a 38-10 loss at Miami.

Laying 5 touchdowns or more at this point of the season feels like a fool’s errand, but I have to imagine Notre Dame wants to run up the score to ensure the CFP committee doesn’t drop the Irish out of the playoff. After all, the Irish do not have the benefit of playing in a conference championship. Look for them to roll at home against a Syracuse team that doesn’t have much to play for over its final 2 weeks.

Syracuse vs Notre Dame prediction: Notre Dame Fighting Irish -35.5 (-110) at the time of publishing. Playable at that number or better.

You can bet on our Syracuse vs Notre Dame pick with BetMGM, where right now new users can activate your new BetMGM account ⚡ and receive $150 in bonus bets INSTANTLY if your first $10+ wager is a winner!