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The 2025 NFL season is finally here, and so is the action for bettors across the country. Week 1 brings not only high-stakes matchups but also great opportunities to cash in against the spread (ATS). With offseason hype, rookie debuts, and fresh coaching schemes, early weeks can be unpredictable—but also incredibly profitable.
We’ve analyzed expert picks, early odds, and betting trends to bring you the Top 5 NFL Picks Against the Spread for Week 1 (2025).
🦅 1. Philadelphia Eagles –7 vs. Dallas Cowboys
Pick: Eagles to cover –7
Why: Philadelphia opens as defending Super Bowl champs at home, a spot where favorites typically dominate. With Jalen Hurts healthy and a stacked defense, Philly is primed to make a statement.
Trend to Watch: Super Bowl winners are 15–5 SU in Week 1 since 2004.
🐯 2. Cincinnati Bengals –5.5 at Cleveland Browns
Pick: Bengals to cover –5.5
Why: Joe Burrow is back and healthy, while the Browns face uncertainty at QB. Cincinnati’s firepower should be too much for Cleveland’s inconsistent offense.
Betting Edge: Bengals 6–2 ATS in last 8 road openers.
🐾 3. Carolina Panthers +3.5 at Jacksonville Jaguars
Pick: Panthers +3.5
Why: Carolina is a live dog with Bryce Young entering Year 2 and a rebuilt offensive line. This has all the makings of a trap game for Jacksonville.
Key Stat: Underdogs are 71% ATS in Week 1 divisional games over the past 5 years.
🐦 4. Arizona Cardinals –3.5 at New Orleans Saints
Pick: Cardinals to cover –3.5
Why: Arizona has quietly built a solid squad around Kyler Murray. Meanwhile, New Orleans enters the season with major QB uncertainty after Derek Carr’s retirement.
Watch Factor: Arizona’s defense ranked top 10 vs. the run last season.
🐬 5. Miami Dolphins +1.5 at Indianapolis Colts
Pick: Dolphins +1.5
Why: The Dolphins’ speed on both sides of the ball gives them the edge indoors. With Tua Tagovailoa fully healthy, Miami could steal this one outright.
ATS Note: Miami is 9–3 ATS in their last 12 road games as underdogs.
✅ Quick Recap: Week 1 ATS Picks
| Matchup | Pick |
|---|---|
| Cowboys @ Eagles | Eagles –7 |
| Bengals @ Browns | Bengals –5.5 |
| Panthers @ Jaguars | Panthers +3.5 |
| Cardinals @ Saints | Cardinals –3.5 |
| Dolphins @ Colts | Dolphins +1.5 |
🧠 Betting Strategy Tip for Week 1
Week 1 is full of unknowns, which means market inefficiencies. Focus on:
Teams with coaching continuity
Veteran QBs vs. new systems
Public overreaction to preseason hype
