NFL Week 1 odds, predictions: Picks, best bets from 10,000 computer sims

The NFL never shies away from loading up the opening week with must-see matchups, and the Week 1 NFL schedule, which begins in just four days, is no different. From divisional battles like the primetime matchups of Chiefs vs. Broncos (+2.5) and Cowboys vs. Giants (+3) to Aaron Rodgers’ last ride in Steelers vs. Falcons (+3.5), you have a bevy of intriguing options to place Week 1 NFL bets on. Meanwhile, Dolphins vs. Raiders is a matchup that may not garner as much interest as the aforementioned, but it still carries intrigue for Week 1 NFL picks as the only opening game guaranteed to have two new starters under center. Bet NFL games at DraftKings. Claim their new user offer here:

Miami’s Malik Willis will duel with Kirk Cousins, as the veteran gets the starting nod over Fernando Mendoza. Vegas, who went 7-10 ATS last year, is a 3.5-point favorite per the latest Week 1 NFL odds. All of the updated Week 1 NFL lines are listed below, and SportsLine’s advanced computer model has all the NFL betting advice and NFL predictions you need to make the best Week 1 NFL picks now.

The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on betting sites on top-rated NFL picks since its inception. The model enters the 2026 NFL season on a 53-37 run on top-rated picks dating back to 2024. Anybody following its picks at NFL betting sites could have seen strong returns.

Now, it has turned its attention to the latest Week 1 NFL odds and NFL betting lines and locked in betting picks for every NFL matchup. Head here to see every pick.

Top Week 1 NFL predictions

We can tell you one of the model’s strongest Week 1 NFL picks for the best betting apps is that the Jaguars (-7.5, 40.5) cover at home versus Cleveland in a Sunday 1 p.m. ET kickoff. The model has the Jags prevailing versus the spread nearly 60% of the time, continuing the success they had last year with a league-best 12-5 ATS mark in the regular season. Jacksonville was even more proficient versus the line at home, covering in 78% of games, also the best record in the NFL, while Cleveland was 2-6 ATS on the road, which was the second-worst mark in the NFL. SportsLine’s model also has the Over hitting in 64% of simulations. See which other teams to pick here.

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Another one of its Week 1 NFL predictions: the Eagles (-5.5, 44.5) cover versus the Commanders on Sunday at 4:25 p.m. ET. Philadelphia has won eight of its last nine versus Washington in games that Jalen Hurts has started and finished. He should have continued production versus Washington’s defense which ranked dead last in yards allowed last year and is in transition, with up to eight new starters and moving from a 4-3 base to a 3-4. Add in that Jayden Daniels may use his legs less to avoid the injuries he suffered in 2025, and the fact that Commanders left tackle Laremy Tunsil (triceps) is out, and Philly is forecasted to cover the spread in nearly 60% of simulations in an A-rated pick. See which other teams to pick here.

How to make Week 1 NFL picks

The model has also made the call on who wins and covers in every other game on the Week 1 NFL schedule and just revealed multiple underdogs that outright win, potentially giving you a huge payday. You can only get every pick for every game at SportsLine.

So what Week 1 NFL picks can you make with confidence, and which underdogs should you lock in now? Check out the latest NFL odds below, then visit SportsLine to see which teams win and cover the spread, all from a proven computer model that has returned well over $7,000, and find out.