NFL Week 1 Picks & Predictions 2025: Straight-Up and ATS for Every Game

NFL Week 1 Is Finally Here

The wait is over. NFL Week 1 kicks off with a weird but fun schedule twist — a Super Bowl rematch on Wednesday night, followed by the league's first-ever Australia game on Thursday. From there, it's a full slate of matchups that'll set the tone for the entire 2025 season.

If you're into betting, fantasy, or just want to know who's favored before you settle in for Sunday football, here's the full breakdown of straight-up and against-the-spread picks for every Week 1 game.

The Marquee Matchups

The Seahawks open things up against the Patriots on Wednesday night, and the pick is Seattle to win outright — though New England covers as home dogs at +3.5. Over in Australia, the Rams are expected to handle the 49ers both straight-up and against the spread, a solid early signal for L.A.'s season outlook.

One of the more eyebrow-raising calls this week: the Packers are picked to lose outright to the Vikings, with Minnesota also favored to cover. That's a tough spot for Green Bay fans expecting a bounce-back year, and it's exactly the kind of Week 1 stunner that shifts early season narratives fast.

Upset Watch and Value Picks

A few spots stand out for bettors looking for value. The Saints are picked to cover against the Lions even in a projected loss, landing at +6.5. The Jets are favored to beat the Titans outright, a mild surprise given recent history between these two rosters. And the Bears are tabbed to both win and cover against the Panthers, suggesting some real optimism building in Chicago.

Meanwhile, defense-driven picks continue to dominate divisional and conference battles — the Ravens, Eagles, and Bengals are all favored to win comfortably, reinforcing that the league's usual contenders are picked to start strong.

Why Week 1 Picks Actually Matter

Week 1 predictions aren't just about bragging rights. They set the baseline for how bettors, fantasy managers, and fans recalibrate expectations heading into the season. A stunner like the Packers-Vikings pick can shape power rankings, playoff odds, and even trade speculation for weeks. And these picks come from a track record that finished last season 170-115 straight-up, so there's real data-backed reasoning behind the calls — even when they lean toward an upset.

What to Watch For

Keep an eye on how the underdogs perform against the spread rather than just who wins outright — several of this week's ATS picks favor the team expected to lose, which tells you a lot about how tight oddsmakers think these games will be. Whether you're filling out a survivor pool, building a fantasy lineup, or just want bragging rights at your Week 1 watch party, these picks give you a full-slate cheat sheet before kickoff.