The 2025 NFL season begins this weekend, with a full batch of pre-season American football scheduled between Thursday and Sunday.
And while we may not see all the veteran starters take the field, the rookies and young roster hopefuls should provide for plenty of entertainment and betting interest.
The Eagles kicked off their Super Bowl title defense on Thursday evening with a 34-27 win over the Bengals in Philadelphia.
The reigning AFC North-champion Ravens were also active on opening night of pre-season, besting the Colts 24-16. And the Seahawks played former head coach Pete Carroll and his Raiders to a 23-23 tie in Seattle.
On Friday, most eyes will be on the Lions vs. Falcons in Atlanta, with Detroit looking to rebound from a miserable Hall of Fame Game loss to the Chargers. At about the same time, second-year quarterback Drake Maye and the Patriots will clash with the Commanders in New England.
Hours before that kick-off, another QB named Tom Brady will have his statue unveiled outside Gillette Stadium.
Moving on to Saturday, the Texans and Vikings — two playoff teams last winter — will clash in Minnesota in the late-afternoon game. Then the Cowboys will battle the Rams in LA, the Steelers will take on the Jaguars in Florida, the Jets will travel to Green Bay to face the Packers and the reigning AFC-champion Chiefs will collide with the Cardinals in Arizona.
The last game of the night, the 49ers vs. Broncos, might be one of the better tilts of the weekend.
The weekend wraps up with a doubleheader on Sunday, starting with the Dolphins at Bears followed by the Saints at Chargers. Chicago has its sights set on a much-improved season under former Lions offensive coordinator Ben Johnson, while Jim Harbaugh's Chargers look to make a leap into Super Bowl contention with some solid young additions.
Let's take a look at the best bets for opening weekend of the 2025 NFL pre-season, including the top moneyline, spread and over/under betting picks courtesy of our U.S. betting expert Sloan Piva.
MORE: Early 2026 Super Bowl odds and favourites ahead of new NFL season
NFL Preseason Week 1 2025 best bet: Moneyline
All odds correct as of Friday.
Lions (8/11) halftime at Falcons (Paddy Power)
The Lions have already played a game this pre-season — they got boat-raced 34-7 by the Chargers in the Hall of Fame Game. Detroit head coach Dan Campbell has probably already addressed the big issues from that game, and will likely want his squad to rebound from the whooping and make an early statement in Atlanta.
Of course, it helps that Falcons QBs Michael Penix Jr. and Kirk Cousins will both be inactive on Friday. Easton Stick and Emory Jones probably can't take a hungry Lions squad down, especially in a game that NFL Network will be televising live. Word around Detroit has been that the Lions' D, especially the secondary, has been on point since the first preseason game. Time to cash in.
NFL Preseason Week 1 2025 best bet: Against the spread
Patriots -6.5 vs. Commanders (1/1, Betfair)
Yours truly has been around the Patriots camp this offseason, and let's just say that the buzz has reached levels New England hasn't experienced since Tom Brady left town. Fitting, then, that the Pats win their first preseason game on the same day the organization unveils the Tom Brady statue outside Gillette Stadium.
Jayden Daniels and the Commanders were the talk of the NFL world for most of last season. It's quite possible Drake Maye and the Patriots take over as the most exciting (and most improved) young squad in the league. And, for what it's worth, Daniels and multiple key Commanders won't be playing on Friday night.
Pats head coach Mike Vrabel and offensive coordinator Josh McDaniels have plenty of young talent to support Maye, including a retooled offensive line, stud rookie back TreVeyon Henderson, and rookie receivers Kyle Williams and Efton Chism. Take the Pats at home and double your money.
NFL Preseason Week 1 2025 best bet: Over/under total
Saints UNDER 19.5 total points at Chargers (3/4, BetVictor)
Did you catch how fantastic the Chargers looked in their pre-season opener against the Lions? They racked up three interceptions, two fumble recoveries and two sacks, and they held Detroit to just one third-down conversion on 11 attempts.
Now LA draws a home game against Tyler Shough, Spencer Rattler and the Saints. No matter how positive Kellen Moore spins that QB room, it's one of the worst situations in the NFL. Los Angeles probably won't let New Orleans even sniff 20 points on Sunday.
NFL Preseason Week 1 2025 best bet: Game prop
Chiefs -0.5 1st-quarter spread at Cardinals (23/20, Betfair)
It has already been reported that two-time MVP and three-time Super Bowl MVP Patrick Mahomes will play the first quarter of the Chiefs vs. Cardinals game in Arizona. Thus, Kansas City seems like a good bet to win that opening frame.
With wideout Rashee Rice banged up and facing a likely suspension to start the season, Mahomes will need to establish a strong early connection with young speedy receivers like Xavier Worthy, Jalen Royals and Tyquann Thornton. Running back Isiah Pacheco will also need to prove that he's back to being a difference-maker after an injury-ravaged and frustrating 2024 season.
Arizona is far from a strong defense – PFF graded it a bottom-10 unit last year — and with six new starters, it might endure some growing pains against the reigning AFC champs. Go with Kansas City to win the first quarter.