The 2025 NFL regular season launches Thursday with the Philadelphia Eagles (-8.5) hosting the Dallas Cowboys. Week 1 spans from Thursday to Monday, with notable games including a Friday international matchup in São Paulo between the Kansas City Chiefs (-3) and Los Angeles Chargers, and a Sunday Night contest featuring the Baltimore Ravens against the Buffalo Bills (-1.5).
Key matchups like Lions (-2.5) facing Packers and 49ers (-2.5) meeting Seahawks are also highlighted.
Before placing any bets, check the NFL against the spread and over/under picks powered by the SportsLine computer simulation model which simulates every game 10,000 times.
The model shows significant success, generating over $7,000 in profit for $100 players on top-rated bets since its inception, recording a 31-15 success rate on top picks last season.
For detailed NFL betting insights for Week 1, the model has evaluated all NFL odds and presented picks for all 16 games.
Top Week 1 NFL Picks: The Commanders are favored as 6-point home favorites against the Giants, with projections indicating the game will go Over a total of 45.5 in nearly 70% of simulations.
The Commanders feature a promising young quarterback, Jayden Daniels, the 2025 NFL Offensive Rookie of the Year, along with newly acquired All-Pro receiver Deebo Samuel. Their defensive lineup is further strengthened by Super Bowl MVP Von Miller.
Visit SportsLine for additional predictions and picks!
