The 2025 NFL regular season kicks off on Thursday, with the defending Super Bowl champion Philadelphia Eagles (-8.5) hosting the Dallas Cowboys in the 2025 NFL Kickoff Game. Week 1 spans Thursday through Monday, highlighted by a Friday international matchup in São Paulo between the Kansas City Chiefs (-3) and Los Angeles Chargers, and a Sunday Night Football showdown featuring the Baltimore Ravens against the Buffalo Bills (-1.5). The opening weekend also features heavyweight matchups like the Lions (-2.5) vs. Packers and 49ers (-2.5) vs. Seahawks.

Who should you back in each of the 16 games on the Week 1 NFL schedule, and how should you handle all your NFL money line, NFL over/under and NFL against the spread spread picks? Before making any Week 1 NFL picks or Week 1 NFL score predictions, you need to see the NFL against the spread, NFL over/under, and NFL money-line predictions powered by the SportsLine computer simulation model.

The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on top-rated NFL picks since its inception. The model went 31-15 on top-rated picks in 2024. Anyone following has seen huge returns.

For Week 1 NFL betting, the model has evaluated the NFL odds and provided picks for all 16 games. You can only see the simulation model's predictions for the Week 1 NFL schedule here. Also, can also target the DraftKings promo code, which offers $300 in bonus bets instantly plus over $200 off NFL Sunday Ticket:

Top Week 1 NFL simulation picks

After analyzing every game in Week 1, the model says the Commanders cover comfortably as 6-point home favorites against the Giants on Sunday in a game the model projects will go Over the total (45.5). The Commanders are coming off a surprise run to the NFC Championship Game last year, and enter the 2025 season with championship expectations. DraftKings Sportsbook lists Washington with a projected regular season win total of 9.5.

The Commanders are paced by one of the top young quarterbacks in the NFL in Jayden Daniels. The reigning NFL Offensive Rookie of the Year was outstanding in 2025, and Washington gave him another explosive weapon during the offseason in All-Pro wide receiver Deebo Samuel. Defensively, the Commanders also boast one of the premier front sevens in the league -- a group that was bolstered by the offseason addition of Super Bowl 50 MVP Von Miller. See its other Week 1 predictions and football picks at SportsLine.

How to make Week 1 NFL computer picks

In addition, the model has generated three other highly-coveted A-graded picks for Week 1, which includes an underdog winning outright on the moneyline. You can only see the model's picks and analysis at SportsLine.

Who wins and covers each Week 1 NFL game, and which A-graded picks should you target now? Visit SportsLine now to see the top NFL against the spread, over/under, and moneyline picks, all from the computer simulation model that is up over $7,000 since its inception, and find out.