49ers vs. Seahawks Picks: Key Week 1 Matchup Insights

Sam Darnold leads the Seahawks as their starting QB this season - 49ers Seahawks Picks

The NFL season officially kicked off last night, but this Sunday we have a weekend full of action on the gridiron. In the later slate, we head to the Pacific Northwest as two NFC West teams go head to head in a divisional showdown. The new look Seattle Seahawks host the San Francisco 49ers who seem to be limping into the season once again. The 49ers went from Super Bowl Runner Ups to dead last in the division in just one season, and I’ll be the first to admit that was probably due to all of their injuries. Let’s get into these two teams and find our favorite picks as the Seahawks take on the 49ers.

Check out the latest odds at the best online sportsbooks. Plus, take some time to check out our NFL Divisional Previews below.

San Francisco 49ers vs. Seattle Seahawks NFL Betting Insights

Brock Purdy leads the 49ers into this divisional game in Seattle

Not only are the 49ers beat up, but they have several guys sidelined as well. For starters, that team that went to the Super Bowl two years ago? They had Deebo, Brandon Aiyuk and a healthy CMC. None of those pieces exist for the 49ers anymore.

Brock Purdy still leads the offense, you still have George Kittle at TE and Trent Williams at LT. But Deebo is no longer with the team, Brandon Aiyuk is injured for a good portion of the season, and even CMC and Jauan Jennings were limited in practice on Thursday and remain questionable for Sunday’s road opener. This division is absolutely wide open, and I could really see any of the four teams winning the title at the end of the season.

But I do have beans on the Seahawks. I’ve got faith in this team. Yes, they have a new head coach and tons of new offensive pieces. But I am a believer in the resurrection of Sam Darnold, and I think he will lead Seattle to a solid season. He pairs up with Kenneth Walker at RB, as well as Cooper Kupp and Jaxon Smith-Njigba to catch passes. I’ll admit, after that, the Seattle skill players see a significant drop in talent, but defensively I think this team can compete.

Plus, I’ve got to lean with the home divisional underdog.

Christian McCaffrey was limited in practice on Thursday, and his status for Sunday is questionable

Matchup Information – 49ers vs. Seahawks

Venue & Location: Lumen Field (Seattle, WA)
Date: Sunday, September 7, 2025
Kick Off: 4:05 p.m. Eastern
Broadcast: FOX

49ers vs. Seahawks Betting Odds – September 7

Odds are courtesy of BetOnline, one of our favorite online sportsbooks as of September 5, 2025, at 8:01 a.m. eastern. Sign up today with Promo Code FREE250 for a 50% deposit bonus up to $250 as well as 100 Free Spins at the online casino.

Spread

49ers -2 (-110)
Seahawks +2 (-110)

Moneyline

49ers -129
Seahawks +109

Total

Over 43 (-110)
Under 43 (-110)

San Francisco 49ers vs. Seattle Seahawks Picks and Predictions

Kenneth Walker has a new QB in Seattle. Will their offense elevate to the next level?

49ers vs. Seahawks NFL Prediction: Seahawks Win Outright, Under 43

Best Bet: Seahawks +2 (-110) BetOnline

I am high on the Seahawks this season and low on the rest of the NFC West. Plus, I’m interested in backing plenty of home, divisional underdogs this season, even though I am passing on a few in Week 1. These teams have plenty of history, Seattle lost at home to San Francisco last season, losing by 12, but got their revenge and beat them by three on the road.

I see Seattle successfully defending their home field this weekend.

Despite starting 4-5, the Seahawks finished 6-2 last season with much of their current defense. Offensively, this team will certainly be more potent than last season, as I trust Darnold’s performance last year not to be a fluke. Taking it even further with Darnold, last season he got to play with one of the best defenses in the NFL. While I have faith in the Seahawks defensive unit, they certainly will not compare to that of the Vikings, meaning Seattle will rely more heavily on Darnold and the offense to put up points on the board.

On the San Francisco defensive side of things, they lost plenty of talent in their secondary, which could lead to wide open targets for Kupp and JSN. Darnold has had plenty of time to get used to this new offense and build chemistry with his pass catchers, and I see them surprising some people this season, and on Sunday.

I like Seattle to win outright, but taking the points is enough for me.

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San Francisco 49ers vs. Seattle Seahawks Picks and Predictions: Divisional Showdown in Week 1