NFL Picks Against the Spread for Every Week 1 Game

Now that we know all the 2025 NFL season matchups, we're as excited to get to work as all the new head coaches. As part of the NFL picks, here are our early NFL picks against the spread (ATS) for Week 1 of the 2025 NFL season. 

👉 Check out our 2025 NFL season AI predictions

🏈 Early NFL ATS picks Week 1: Every game

NFL odds via FanDuel and subject to change; pick confidence based on a 1-to-5-star scale.

My favorite ATS picks for Week 1 

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Panthers vs. Jaguars (-2.5)

Best odds: -115 via FanDuel | Implied probability: 53.49%

The Carolina Panthers had the worst scoring defense in NFL history last season, allowing 31.4 points per game. While adding Bobby Brown III, Tershawn Wharton, and Tre'von Moehrig will invariably help, their pass rush remains about as inspiring as Dave Canales' coaching.

Bryce Young was granted a stay of execution in the Deep South after throwing seven touchdowns and no interceptions in the final three weeks of last season, which should offer Panthers' fans a glimmer of hope. With all eyes on the previously embattled quarterback, Young has a lot to prove. 

The Jacksonville Jaguars, however, should be one of the most improved teams. Led by new head coach Liam Coen, who impressed last season as the Tampa Bay Buccaneers offensive coordinator, and a healthy Trevor Lawrence, the Jaguars will be rejuvenated entering Week 1.

With Brian Thomas Jr. and 2024 Heisman Trophy winner Travis Hunter to target, Lawrence should have his way with the Panthers' subpar pass rush. Plus, Lawrence has Travis Etienne and Tank Bigsby as his two-headed backfield threat against a team that ranked last by PFF in run defense last season. 

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Cardinals (-3.5) vs. Saints

Best odds: -110 via DraftKings | Implied probability: 52.38%

I can't get on board with a New Orleans Saints team with arguably the worst quarterback room in the league. The Cleveland Browns have a solid claim on that dubious title, too. Derek Carr and his disintegrating shoulder left the Saints in the lurch.

I don't envy new head coach Kellen Moore. The Saints are in trouble regardless of who the offensive-minded head coach tosses into the line of fire (Spencer Rattler, Jake Haener, or second-round pick Tyler Shough).

Meanwhile, the Arizona Cardinals enjoyed a terrific start to last season before fading down the stretch. Marvin Harrison Jr. should be better in his sophomore year, and Kyler Murray has the improvisation skills and athleticism to offset some of his offensive line's deficiencies. 

Adding Dalvin Tomlinson and Calais Campbell will improve Arizona's run defense, while edge-rusher Josh Sweat will add pressure, and cornerback Will Johnson will buoy the pass defense. That's more than enough to take care of business against a downtrodden Saints team.

DraftKings is currently the only one of our best sports betting sites offering -3.5. The others have them as 4.5-point betting favorites. 

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Texans vs. Rams (-2.5)

Best odds: -115 via BetMGM | Implied probability: 53.49%

The Los Angeles Rams got healthy at the right time last season and finished the campaign with a 7-1 ATS record, including the heartbreaking playoff loss in Philly to the Eagles.

Their lone ATS defeat in that stretch came in a meaningless Week 18 game against the Seattle Seahawks, in which they rested several key starters. 

The Rams added Davante Adams while losing Cooper Kupp, and Stafford has Kyren Williams, one of the league's best running backs, to help take the pressure off. They also have one of the most promising young stop units, featuring Defensive Rookie of the Year winner Jared Verse and Braden Fiske, who thrived toward the end of the season.

Meanwhile, the Texans have almost made wholesale changes to an offensive line that allowed 54 sacks last season, tied for the third most. While the re-jigged offensive line might be better, I can't see it gelling from Week 1, which Stafford will take advantage of. 

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🔮 2025 NFL season previews & predictions

Following the NFL schedule release, we broke down the odds for every game and asked AI to predict every game (and more). Below are our team-by-team schedules, odds, and predictions for Week 1 through Week 18.

• NFL Week 1 odds and schedule
• NFL Week 1 picks against the spread
• NFL International schedule and odds
• NFL Thanksgiving schedule and odds
• NFL Christmas schedule and odds
• NFL Week 18 odds and schedule
• Best revenge games for the 2025-26 season

NFL betting odds pages

Here are our best NFL betting sites:

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