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 sc

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