2025 NFL Week 1 Picks, Betting Predictions & Best Bets To Back: Let The Games Begin

Week 1 of the 2025-26 NFL betting season brings renewed hope (and delusion) for all 32 franchises.

The reigning Super Bowl champion Eagles kick things off at home Thursday, Sept. 4, against NFC East rival Dallas. Philly enters the season with a new OC. The Cowboys enter with a new head coach — Brian Schottenheimer, who replaced the perpetually perplexed Mike McCarthy.

RELATED: Super Bowl 60 Odds

The next night, the Los Angeles Chargers “play host” to the Kansas City Chiefs in Sao Paolo, Brazil. Yes, Brazil. The game will stream exclusively on YouTube — a first for the league.

Last year, the Eagles posted the NFL’s best record at 14-7 against the spread. That tied in terms of winning percentage the Broncos, Chargers, and Lions at 12-6.

Sunday’s national CBS game at 4:25 p.m. ET features the Detroit Lions at Green Bay Packers. The Sunday night capper? Baltimore Ravens at Buffalo Bills — their third meeting in a year. Monday night closes with an NFC North clash featuring the Minnesota Vikings at Chicago Bears.

2025-26 NFL Week 1 Best Bets: Odds & Picks

Now it’s on to our Week 1  NFL picks to back on your favorite sports betting app. 

2025-26 NFL Week 1 Best Bets: Game-By-Game Analysis

Thursday, September 4
Dallas Cowboys at Philadelphia Eagles, 8:20 p.m. (NBC)

Buzz: Philly unveils its revamped lineup and hangs its Super Bowl 59 banner. Dak, Jalen, Saquon and A.J. Brown return, but both teams retooled their trenches. Brian Schottenheimer takes over as HC in Dallas. Rest easy Mike McCarthy. Two teams. One trophy. One hangover. But not tonight.b

Best Bet: Eagles -7 (-105) at BetRivers via OddsJam

Friday, September 5
Kansas City Chiefs vs. Los Angeles Chargers, 8 p.m. (YouTube)

Buzz: In what will be an NFL first, this game will be streamed exclusively on YouTube and available free to a world-wide audience. The Chargers are the "home team" in Sao Paolo, Brazil. The Chiefs are still trying to figure out what hit them in Super Bowl 59. The Chargers begin Year 2 under Jim Harbaugh with realistic hopes of finally ending Kansas City's run at 8-time defending AFC West champions. The last team to turn the ball over loses. The Chargers defense will be the surprise here as many as 1 billion people log-in to take a peek at this game. Especially for those around the world whose NFL knowledge is limited to Patrick Mahomes (above), Travis Kelce, and Taylor Swift. 

Best Bet: Under 44.5 Points (-105) at FanDuel via OddsJam

Sunday, September 7
Pittsburgh Steelers at New York Jets, 1 p.m. (CBS)

Buzz: Could this be Aaron Rodgers' homecoming to MetLife? He appears to be nearing a deal to sign with the Steelers with each passing post on X or appearance with Pat McAfee. The Jets moved on to Justin Fields at QB. The Steelers QB room looks like something out of the XFL wavier wire. Give us A-Rod lighting up Gang Green for 3 TDs and 320 yards passing. 

Best Bet: Under 39.5 Points (-110) at DraftKings via OddsJam 

Tampa Bay Buccaneers at Atlanta Falcons, 1 p.n. (FOX)

Buzz: Atlanta wisely loaded up on defense in the draft, taking Georgia's Jalon Walker and Tennessee's James Pearce Jr. in the first round. But it's too early to expect big dividends from these 2 potential cornerstone players. Is it too early to call this an NFC South elimination game? Nope. Michael Penix Jr. begins his first full season under center for Atlanta and its wannabe high-scoring offense. Tampa returns most of the gang, with Baker Mayfield, Mike Evans, and Chris Godwin leading the charge. Track meet alert.

Best Bet: Buccaneers -1.5 (-115) at BetMGM via OddsJam 

Carolina Panthers at Jacksonville Jaguars, 1 p.m. (FOX)

Buzz: A pair of NFL stray cats square off in Duval County. NFL bettors and analysts wax rhapsodically about "weather games" late in the season. The "Frozen Tundra." Or all that lake-effect snow in Cleveland and Buffalo. Or below-zero temperatures in Kansas City. All the stuff of legend. Let's show some love for 92 degrees, with a 101-degree heat index and 89% humidity. Welcome to the sweatiest game of the year. Forget snow — early September Florida heat and humidity is brutal. Carolina may wish for a hurricane delay. Jacksonville won’t be so forgiving.

Best Bet:  Jaguars -3.5 (-110) at Caesars Sportsbook via OddsJam 

Cincinnati Bengals at Cleveland Browns, 1 p.m. (FOX)

Buzz: The Cleveland Browns get to showcase two-way, All-World SuperStar Travis Hunter. The Browns have 5 QBs on their preseason roster, including Hunter's former Colorado teammate Shadeur Sanders. Five QBs? That’s not depth — that’s desperation. Burrow and the Bengals need a statement win. Hunter may be flashy, but who’s throwing him the ball? Besides Burrow? Not Joe Flacco. We think? 

Best Bet: Bengals -5.5 (-105) at FanDuel via OddsJam 

Miami Dolphins at Indianapolis Colts, 1 p.m. (CBS)

Buzz: Tyreek Hill laughed at the Colts’ “Coast Guard” social media post. He won’t laugh at Indy’s defense.Miami’s offense is evolving to keep Tua upright. Colts QB Anthony Richardson must prove he can finish what he starts.

Best Bet: Dolphins +1.5 (-105) at BetMGM via OddsJam 

Las Vegas Raiders at New England Patriots, 1 p.m. (CBS)

Buzz: Welcome to Homecoming Week in Foxboro. Patriots Hall of Fame QB and Las Vegas Raiders part-time owner Tom Brady will NOT be at Gillette Stadium. He'll be calling one of the games on FOX. But former Raiders coach Josh McDaniels is running the Patriots' offense for Mike Vrabel. The third Patriots coach in 3 years, Vrabel has cleaned house since taking over for Jerod Mayo. Vrabel won 3 Super Bowls playing for the Patriots and caught 11 passes - all TDs - from Brady. Drake Maye gets the keys to the kingdom. Across the field, Pete Carroll returns to New England as the NFL’s oldest coach. The "new" Raiders coach helmed the Patriots 1997-99. And was replaced by one Bill Belichick. Circle-of-life stuff.

Best Bet: Patriots -2.5 (-105) at BetRivers via OddsJam

Arizona Cardinals at New Orleans Saints, 1 p.m. (CBS)

Buzz: The Saints have a QB problem. The Cardinals don’t — for once. New HC Kellen Moore inherits a project in New Orleans. Arizona can start 4-2 with a win here. Take flight.

Best Bet: Cardinals -3.5 (-118) at DraftKings via OddsJam 

Tennessee Titans at Denver Broncos, 4:05 p.m. (FOX)

Buzz: Cam Ward makes his NFL debut as a rookie starting QB in the not-so-friendly confines what most of know as Mile High Stadium in Denver. He'll face a challenge of both altitude and attitude. Sean Payton's team will be ready. The Broncos were tied with 3 other teams (Detroit, Washington, LA Chargers) for the best winning percentage (66.6%) ATS last season. Titans rookie and No. 1 overall pick QB Cam Ward starts in Denver — where dreams and oxygen go to die. Ward played at Washington State in the old Pac-12 before transferring to Miami, so he's used to playing at elevation. But he's never faced a road NFL crowd whose team finally has a shot to win the AFC West. The Broncos’ defense is nasty. Payton’s squad was 4-0 ATS as 7+ point favorites last year. Don’t overthink it.

Best Bet: Broncos -7 (-115) at FanDuel via OddsJam 

San Francisco 49ers at Seattle Seahawks, 4:05 p.m. (FOX)

Buzz: Brock Purdy got his bag, going from "Mr. Irrelevant" to the "$265 Million Man." Bleacher Report ranks the 49ers' offense as second-best in the NFL, only behind Baltimore. Why? Kyle Shanahan has a full tool box. Running back Christian McCaffrey, WR Brandon Aiyuk (the subject of multiple trade rumors), TE George Kittle, LT Trent Williams and Purdy all missed time last season due to injury. Expect them back healthy in Week 1. The team still boasted a Top 5 offense last season. Many see the 49ers as one of the NFL's top potential comeback stories. Seattle’s offense? Still a work in progress. Don’t let the mild West Coast vibes fool you — this could get ugly fast.

Best Bet: 49ers -1 (-110)  BetRivers at OddsJam

Detroit Lions at Green Bay Packers, 4:25 p.m. (CBS)

Buzz: The national game of the week on CBS has the Detroit Lions visiting their long-time NFC North rivals in Green Bay. Both teams fell short of their own expectations last season. The Lions were throttled by the Commanders 45-31 in the Divisional Round of the playoffs last season at home, after defeating Tampa Bay a week earlier. The Packers were knocked out in the Wild Card Round. Jared Goff has his full arsenal. Detroit got perhaps the biggest upgrade in the offseason by having former No. 2 pick and DE Aidan Hutchinson back after his season-ending leg injury suffered in Week 5. Two of Jordon Love's projected top-three receivers are potentially questionable to start the season and the third is rookie Matthew Golden. Not a good matchup against this Lions defense - even at home. This one sets the tone for the NFC North. 

Best Bet: Lions ML -115 at ESPN BET via OddsJam 

Houston Texans at Los Angeles Rams, 4:25 p.m. (CBS)

Buzz: Two conference championship contenders meet at SoFi Stadium. The Texans (11-8 and 8-9-2 ATS last season) won the AFC South and are still recovering - emotionally at least - from their "we had it in the bag" loss to the Kansas City Chiefs in the playoffs. The Rams (10-7 and 11-8 last season) took the NFC West last season and bounced Minnesota in the Wild Card Round before coming up short in a 28-22 loss to the eventual Super Bowl champs in the Divisional Round. Cooper Kupp is gone, but the Rams plan to implement a high-octane offense around QB Matt Stafford, RB Kyren Williams, WRs Puca Nacua and free-agent acquisition Davante Adams. Houston should enjoy a completely healthy roster, especially concerning Nico Collins and Joe Mixon. The Rams' biggest concern reamins stopping the run. So we know where Houston will be headed with the ball. Houston kicker Ka'imi Fairbairn just needs to keep it straight and through the uprights. 

Best Bet: Texans +3 (-110) at ESPN BET via OddsJam 

Balitmore Ravens at Buffalo Bills, 8:20 p.m. (NBC)

Buzz: "Déjà vu all over again." The AFC's "Game Of The Year" takes place in Week 1. The winner of this game could well enjoy home field against the loser come playoff time. The Bills eliminated the Ravens 27-25 in the Divisional Round at Highmark Stadium. Josh Allen dominated the Ravens in that game, running for a pair of touchdowns and throwing for 2 more, without turning over the ball. But Allen and Bills then failed - again - to get past Kansas City. These versions of the Ravens and Bills appeared to have peaked. This one's gonna be good. Buffalo’s new-look receiving corps is a work in progress. So is Lamar Jackson’s playoff karma.

Best Bet: Under 52.5 Points (-120) at BetMGM via OddsJam 

Best Bet: Bills ML (-122) at ESPN BET via OddsJam 

Monday, September 8
Minnesota Vikings at Chicago Bears, 8:15 p.m. (ABC/ESPN)

Buzz: QB J.J. McCarthy makes his injury-delayed debut for the Vikings. The Bears counter with Caleb Williams and a rebuilt offensive line. New HC Ben Johnson gives Chicago a legit offensive mind for once. If Williams has time, look out.

Best Bet: Bears -1 (-110) at Caesars Sportsbook via OddsJam