Week 1 college football picks are in as a busy Sunday features a marquee slate, including No. 9 Ole Miss vs. No. 24 Louisville at 7:30 p.m. ET and a neutral-site showdown between No. 4 Notre Dame and Wisconsin at Lambeau Field. According to the latest odds from major sportsbooks, Notre Dame is a 20.5-point favorite over Wisconsin, and a widely used projection model favors the Fighting Irish to cover in 65% of simulations with a 39-12 outcome.
Week 1 college football picks and best bets
The projection model simulates every FBS game 10,000 times and is riding a 32-19 run on top-rated money-line plays since 2024. For 2026, it has been updated to better account for transfer portal movement when evaluating matchups and betting markets.
Week 1 college football best bets (odds may change)
- Washington State (+23.5) vs. Washington
- Notre Dame (-20.5) vs. Wisconsin
- Under 54.5 in Louisville vs. Ole Miss
Parlaying these three Week 1 college football picks would yield an estimated +585 payout on a $100 stake, based on current market pricing.
Washington State (+23.5) vs. Washington
The Apple Cup renews at 4 p.m. ET. Washington has won eight of the past 10 meetings, but Washington State has covered seven of the last 10 overall and is 6-0 against the spread in its past six as an underdog.
The projection calls for Washington 32, Washington State 16, with the Cougars covering the 23.5-point number in 64% of simulations.
Notre Dame (-20.5) vs. Wisconsin
Notre Dame enters as a College Football Playoff contender and brings back several key starters, including quarterback CJ Carr, who threw for 2,741 yards with 24 touchdowns and six interceptions last season. The Irish paired that offense with a top-15 scoring defense in 2025, allowing 17.6 points per game.
The model projects Notre Dame 39, Wisconsin 12, covering the spread 65% of the time.
Under 54.5 in Louisville vs. Ole Miss
The only Top 25 clash of Week 1 takes place at Nissan Stadium in Nashville, where No. 24 Louisville faces No. 9 Ole Miss. Both defenses were stingy in 2025, each allowing 21.2 points per game or fewer.
Ole Miss returns offensive contributors such as Trinidad Chambliss and Kewan Lacy, but the departures of Lane Kiffin and Charlie Weis Jr. could impact explosiveness. The Under is 4-1 in Louisville’s last five games as an underdog.
The model expects a combined 49 points, giving the Under a 60% edge.
More Week 1 college football picks
These Week 1 college football picks reflect the model’s strongest edges for Sunday’s slate. Bettors should always confirm current lines and monitor injury or lineup updates before placing wagers.
Bettors should also review information from regulated operators and responsible gaming resources such as the American Gaming Association before placing wagers.
