San Francisco 49ers vs Seattle Seahawks Prediction, Preview and Odds - 09/07/2025

Game Time: 4:05 pm ET, Sunday, September 7, 2025

Venue:  Lumen Field, Seattle, WA 

Where to Watch:  FOX

DraftKings:  Point Spread:  49ers -2.5, Seahawks +2.5; Over/Under:  43.5 points

Bet365:  Point Spread:  49ers -2.5, Seahawks +2.5; Over/Under:  43 points

BetMGM:  Point Spread:  49ers -2.5, Seahawks +2.5; Over/Under:  43.5 points

San Francisco 49ers:  0-0 (NFC West)

Seattle Seahawks:  0-0 (NFC West)

Do not miss out on our expert handicapper analysis! Jim Feist is on a HOT STREAK in the NFL on a 105-87-3 NFL RUN for +$7,960 PROFIT! Make sure you check out his picks and many more from the expert handicappers featured in the Shop Picks section.

San Francisco 49ers:  N/A

Seattle Seahawks:  N/A

The 49ers finished last season with a 6-11 record overall and they were 1-5 in their division games too. They had a 4-5 record in their home games and had a 2-6 record in their road games where they will be in this game. Last season, their offense was averaging 22.9 points per game and their defense was allowing an average of 25.6 points per game. Their offense was also averaging 376.3 yards per game and their defense was allowing an average of 317.4 yards per game. Brock Purdy led the team in passing yards with 3,864, Jordan Mason led the team in rushing yards with 789, and George Kittle led the team in receiving yards with 1,106.

The Seahawks finished last season with a 10-7 record overall and they were 4-2 in their division games too. They had a 3-6 record in their home games and had a 7-1 record in their road games where they will be in this game. Last season, their offense was averaging 22.1 points per game and their defense was allowing an average of 21.5 points per game. Their offense was also averaging 332.2 yards per game and their defense was allowing an average of 332.7 yards per game. Geno Smith led the team in passing yards with 4,320, Kenneth Walker III led the team in rushing yards with 573, and Jaxon Smith-Njigba led the team in receiving yards with 1,130.

The current betting odds have the 49ers listed as a 2.5 point favorite in this game according to Draftkings Sportsbook. The 49ers didn't have a good season last year, finishing 6-11 overall and missing the playoffs after years of domination in the NFC West. They did lose in the Super Bowl the year before so they didn't get out to a great start last season, and then they were plagued by many different injuries as nothing was going their way. That down year was more of an anomaly though and they are definitely going to be a lot better this year now that a lot of their key players are healthy again. Meanwhile, the Seahawks had a really good year in their first season under Macdonald as head coach, going 10-7 overall and almost making the playoffs. They have made a lot of changes this season though and they no longer have Geno Smith at QB. Geno Smith wasn't the best option for them, but he did have some really good games for them and there is no guarantee that Sam Darnold is going to be much of an upgrade. Darnold had a great season with the Vikings last year, but he struggled against stronger teams and still hasn't proven himself with just 1 good season under his belt. The Seahawks have also made a lot of other changes to the offense so they could be taking a step back this season after that great year. The 49ers are going to be looking to make a statement in this divisional game to open up the season and show that they are back as a strong force in the NFL. The best way to place a bet here is on the 49ers to cover the spread in this game. 

49ers Seahawks Prediction:  Our NFL Pick for Sunday, September 7, 2025 (4:05 pm ET start time) is 49ers 31 Seahawks 17.

Don't miss our champion handicappers free picks and expert football picks today. And if you enjoyed this San Francisco 49ers Seattle Seahawks prediction, be sure to drop by every day for our weekly NFL predictions and previews.

San Francisco 49ers: 7-4 1H ATS as a road favorite of 7 points or less. 21-15 OVER in all games. 9-5 OVER in a road game where the total is between 42.5 and 49 points. 8-4 OVER versus division opponents.

Seattle Seahawks: 5-12 ATS in home games. 2-6 ATS as a home underdog of 7 points or less. 4-9 ATS in a home game where the total is between 42.5 and 49 points. 147-120 OVER as an underdog.

San Francisco 49ers:  None.

Seattle Seahawks:  None.

“That’s what you hope for. That’s also asking a lot from him. Brock did come into a good situation, where we were at the prime of our team, and that made it a lot easier for him to play at one of the highest levels in the league—I mean the film shows it, everything shows it. But his job gets harder when those guys aren’t there. Now, does that mean he’s got to play better? Yeah, you hope you can elevate his game. Yeah, it puts more pressure on a guy when you don’t have All-Pros in a bunch of spots, but Brock’s the one that can do it. Brock’s the one who I think will play better.” - Kyle Shanahan on Brock Purdy coming into this new NFL season.

"There's an interesting balance of being really proud of the work that we've done and the growth we've had on our team that we felt like we've had, and the balance of the sense of urgency to keep going, and understand that we're not there yet. We'll never be there if we do it the right way, but I feel like the guys have great spirit, I'm really proud of the connection we've built within our team. But it's one of those things where we're always going to be chasing. It's kind of like, the joy in is in the process and in the journey; the destination will take care of itself." - Mike Macdonald on his team this season entering his 2nd year as head coach.

WR Valdes-Scantling, Marquez

WR Pearsall, Ricky

WR Jennings, Jauan

TE Kittle, George

QB Purdy, Brock

RB McCaffrey, Christian

FB Juszczyk, Kyle

WR Smith-Njigba, Jaxon

WR Horton, Tory

WR Kupp, Cooper

TE Barner, AJ 

QB Darnold, Sam

RB Walker III, Kenneth 

FB Ouzts, Robbie

Passing: N/A

Rushing: N/A

Receiving: N/A

Touchdowns: N/A

Passing: N/A

Rushing: N/A

Receiving: N/A

Touchdowns: N/A

Coaches:

San Francisco 49ers: Kyle Shanahan (9th season)

Seattle Seahawks: Mike Macdonald (2nd season)