Fortunately for NFL fans, the wait for the upcoming 2025 season is almost over. The league’s Week 1 slate will commence with a bout between the reigning Super Bowl champion Philadelphia Eagles and Dallas Cowboys on Thursday, and every one of the league’s 32 teams will play in Week 1.
There are some Week 1 matchups that project to be quite lopsided, but there are also contests that could very well be hotly contested with the betting underdogs potentially coming out on top.
Here are three upset predictions for Week 1 of the 2025 NFL campaign with the season opener less than seven days away.
Miami Dolphins @ Indianapolis Colts
Prediction: Dolphins win
ESPN Bet currently has the Colts as 1.5-point favorites to come out on top against a Dolphins team is dealing with some injuries and lost a number of key pieces in the offseason.
However, the Dolphins have never been an easy team to beat in the regular season so long as quarterback Tua Tagovailoa is healthy and serving as the team’s starter. Miami has amassed a 38-24 regular-season record over the years with him as its starting signal-caller, and that’s certainly nothing to sneeze at.
Not only that, but Tagovailoa has a 4-0 record as a starter in Week 1 games over the course of his pro career, and the prediction here is that he will make that record 5-0 soon enough by throwing for 300-plus yards and leading Miami to a double-digit victory on Sept. 7.
While the Dolphins have been a strong Week 1 team in recent years, the same doesn’t go for the Colts. Indianapolis has a record of 0-10-1 across its last 11 season openers, and the squad won’t snap its lengthy streak with a Week 1 victory against the Dolphins.
San Francisco 49ers @ Seattle Seahawks
Prediction: Seahawks win
The 49ers boast a Super Bowl-worthy offensive unit with the likes of quarterback Brock Purdy, tight end George Kittle — who was one of only three players at his position to finish the 2024 season with quadruple digits in receiving yards — and running back Christian McCaffrey leading the way.
But the squad is dealing with some key absences already and will also need to prove that its defense is going to take a step forward after a 2024 season in which it failed to keep points off the board.
With San Francisco going up against a tough Seattle defense, the prediction here is that the 49ers will lose a low-scoring affair despite the fact that ESPN Bet currently has them as 2.5-point favorites.
Seahawks quarterback Sam Darnold will do enough to earn a win in his debut with Seattle after he had a Pro Bowl season with the Minnesota Vikings in the 2024 campaign and threw for 35 touchdowns compared to 12 interceptions.
Detroit Lions @ Green Bay Packers
Prediction: Lions win
Green Bay is a 2.5-point favorite for its matchup against the Lions on Sept. 7 according to ESPN Bet after the team traded for one of the league’s premier defensive players on Thursday. The Packers acquired linebacker Micah Parsons from the Cowboys in exchange for defensive tackle Kenny Clark and a pair of first-round draft picks.
Adding Parsons to a squad that’s on the heels of an 11-win season is a scary thought for the rest of the NFL, but the Lions will prove that they’re still the team to beat in the NFC North by picking up a road win over the Packers.
Detroit finished last season in a tie with the Kansas City Chiefs for the best record in all of football at 15-2, and the prediction here is that the team will look similarly dominant to begin the 2025 season behind a huge scoring game from its offensive unit.
No team scored more points across its 17-game slate than Detroit did in the 2024 season, and the Lions will kick off their campaign by scoring 30 points against a solid Packers defensive unit in a win.
