The San Francisco 49ers begin their 2025 season with a trip to Lumen Field to face the Seattle Seahawks on Sunday.
One of the most profitable NFL betting trends has been backing divisional underdogs in Week 1, and my 49ers vs. Seahawks predictions are taking Seattle with the points. Here are my best NFL picks for this NFC West clash on September 7.
49ers vs Seahawks predictions
Here are our early thoughts on the spread and total for this week’s game. We will have a full game preview (with a best bet and SGP) later in the week.
Early 49ers vs Seahawks spread pick: Seahawks +2.5 (-110)
It can be challenging to predict the first week of the NFL season, and this, combined with the familiarity of inter-divisional rivalries, has led to a profitable trend. Since 2010, divisional home underdogs in Week 1 have gone 23-7 ATS.
The San Francisco 49ers are coming off an ugly 6-11 campaign, and I'm not sure they'll be much better this season. All-Pro RB Christian McCaffrey and LT Trent Williams are healthy to start the year, but the WR corps looks in rough shape.
The Niners had issues attacking downfield last season with Brandon Aiyuk and Deebo Samuel banged up, and both were jettisoned in the offseason. Jauan Jennings will be their No. 1 WR, but has been hindered by a calf injury and sat out August while seeking a contract extension.
They'll have a tough time moving the ball against a Seattle Seahawks defense that made major strides last year under Mike Macdonald. From Week 9 until the end of the regular season, the Seahawks were fifth in the league in defensive EPA and sixth in defensive success rate.
Meanwhile, San Fran's defense was 26th in the league in EPA and 29th in success rate. The Niners lost key players at LB and the secondary in the offseason, while safety Malik Mustapha will start the year on the PUP list. I'll back the team with the better defense catching points at home in Week 1.
Early 49ers vs Seahawks total pick: Under 43.5 (-115)
The Seahawks have a terrific CB duo in Devon Witherspoon and Riq Woolen, and they signed DeMarcus Lawrence to provide more pass rush juice alongside Leonard Williams and Boye Mafe.
With sophomore DT Byron Murphy poised for a breakout year and rookie Nick Emmanwori looking like he'll make an instant impact, this defense could be something special.
That said, Seattle's new-look offense could have problems early in the season. The Seahawks said bye to receivers D.K. Metcalf and Tyler Lockett while Sam Darnold replaces Geno Smith at QB.
Darnold is coming off a career year in Minnesota, but he has to adjust to a new system, and he's stuck behind a brutal offensive line with a weak WR corps.
On the other side of the ball, this Niners defense was bad last year, but expect improvement with Robert Saleh returning as defensive coordinator after four years away. Stars like Nick Bosa and Fred Warner should be able to make this unit respectable at the least.
49ers vs Seahawks odds
- 49ers vs. Seahawks spread: Seahawks +2.5
- 49ers vs. Seahawks moneyline: 49ers -136, Seahawks +116
- 49ers vs. Seahawks Over/Under: 44.5
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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