NFL Week 1 2025: The Toughest Games to Call in the Opening Round

NFL fans do not have much longer to wait until the opening of the 2025 season. They can then look forward to 272 matchups across the fall and winter before getting into the serious business of the Playoffs in January.

Bettors, of course, will be poring over the schedule trying to find value in the NFL Week 1 betting odds. Each game will have hundreds of different props and game betting lines, so there’s always an angle to be found.

Yet, instead of picking out likely winners and betting tips, we wanted to do something different, looking at the games that feel like the hardest to call. In the early season, there is sometimes a sense of teams feeling out the new system, so there can always be a shock or two, but we think the games below are the most difficult to predict on paper, so backing individual player or game props might be the way to go.

Ravens @ Bills

The standout game from the opening week of the season places the two favorites for Super Bowl LX against each other. It’s Lamar Jackson vs. Josh Allen in a battle of the MVP market leaders, too. The Bills have home advantage, so that has allowed them to squeak ahead in the sportsbooks’ betting lines for the game, but, in truth, it feels like a toss-up. We don’t think anyone should get too carried away with victory in this one, as it is a long road to the Playoffs, but it feels like the most significant game of the early season.

Lions @ Packers

DraftKings and other sportsbooks have the Packers at 1.5 on the spread, and that feels just about right for the team at Lambeau Field. The problem with this one is that we do not know what version of the Lions we are going to get. Should it be like the team that dominated across the regular season in 2024, then we’d go for a Lions’ victory (they beat the Packers home and away last season), but there have been changes in Detroit, notably the departure of both the offensive and defensive coordinators, so it remains to be seen whether Dan Campbell can get the same kind of cohesion that blew so many teams away last term.

Chiefs @ Chargers

On paper, most people would say the Chiefs. But this is our first pick on this list that highlights a game that feels like a potential banana skin. Talk of a decline for the Chiefs has been around for a few seasons now, and they keep proving the doubters wrong, but coming into this new campaign, the doubts are there again. The Chiefs won a lot of ugly games last time around – it was almost historic in terms of narrow victories – and rode their luck at times. The Chargers have looked very good in preseason games, and this could be another toss-up at SoFi.

Dolphins @ Colts

Thus far, we have covered matchups between teams with genuine Playoff hopes. This game is hard to call because both teams feel set for mediocre seasons at best. Sportsbooks favor the Colts ever so slightly due to the game being in Indianapolis, but it’s another 50-50 in our book. Neither the Dolphins nor the Colts is the worst team in the NFL this season, but both feel a little bit directionless. Fans of both sets of teams would love to see that sentiment proven wrong.

Buccaneers @ Falcons

We toyed with the idea of putting the Vikings’ visit to the Bears as the last game on this list, but decided on this NFC South clash instead. Personally, we think that the Buccaneers can have a good season, perhaps being the surprise package with a deep, deep Playoff run. But this opening game is a tough one for them. The Falcons beat the Buccaneers twice last season, and they have won four out of the last five against their divisional rivals.