49ers vs Seahawks Predictions, Picks & Best Bets for NFL Week 1

Ducey's prediction: Darnold leads Seattle to a home win in a marquee NFC West clash.

Kenny Ducey - Contributor at Covers
Kenny Ducey • Betting Analyst
Sep 6, 2025 • 18:33 ET • 4 min read

NFL

Match starts: 17 hrs
SEA
38 %
SF
62 %
EXPERT PICK - MONEYLINE
Seattle +100 Seattle +100
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Sam Darnold Seattle Seahawks NFL
Photo By - Imagn Images. Seattle Seahawks quarterback Sam Darnold (14).

The Seattle Seahawks are looking to take things one step further after narrowly missing the playoffs last season, bringing in a new quarterback to inject some life into a talented offense.

They’ll first be pitted against the San Francisco 49ers, coming off an injury-riddled season which saw them finish 6-11.

My 49ers vs. Seahawks predictions will explain why some personnel changes — and injuries — should make life difficult for the road team.

Read more in my NFL picks for Sunday, September 7.

49ers vs Seahawks prediction

49ers vs Seahawks Best bet: Seahawks moneyline (+100)

The San Francisco 49ers are coming off an uncharacteristic season on defense, ranking 22nd in weighted DVOA and just 23rd against the run. While the defensive line did a tremendous job rushing the passer, teams were able to establish the run, and that’s part of what led to a down year.

Now that several key veterans are gone, it’s anyone’s guess what happens next. San Francisco has done its job drafting some young talent up front and signing some veterans, but this is an overall shaky unit that will have a lot to prove — and so does this re-tooled secondary.

That’s where we take a look at the Seattle Seahawks and roll with Sam Darnold in a revenge spot. He’s coming off an excellent campaign where he perfected his deep ball, and while his O-line is in rebuilding mode, we won’t have to worry about a typical 49ers pass rush on Sunday. 

Meanwhile, San Francisco should take a big step back on offense, with three receivers injured — including Brandon Aiyuk — and Deebo Samuel no longer with the team.

There’s plenty to like about this Seahawks offense, so I'm taking Seattle to prevail at home. 

49ers vs Seahawks same-game parlay

It’s going to be a different season for both teams with some personnel changes, and I’ll kick things off by looking at the man who will likely step in to replace Aiyuk.

Ricky Pearsall finished the season strong with 18 targets over his final two games and was on the field for 67.5% of the 49ers' team snaps last year.

Pearsall should see his workload increase on Sunday, as will third-year Seattle back Zach Charbonnet, who faces a Niners team that ranked in the top 10 in receptions allowed to running backs last season.

49ers vs. Seahawks 3-leg SGP

  • Seahawks moneyline
  • Ricky Pearsall o3.5 receptions
  • Zach Charbonnet o1.5 receptions

Our big-ticket SGP: Sam I Am

Darnold threw for 2+ touchdowns in 12 of 17 regular-season starts with the Vikings, and he enters a new-look Seattle offense that projects to pass the ball plenty.

Brian Robinson Jr. is the new man in the San Francisco backfield, and he could see some work at the goal line with Christian McCaffrey nursing an injury.

49ers vs. Seahawks 5-leg SGP

  • Seahawks moneyline
  • Ricky Pearsall o3.5 receptions
  • Zach Charbonnet o1.5 receptions
  • Sam Darnold o1.5 passing touchdowns
  • Brian Robinson Jr. anytime touchdown

49ers vs Seahawks odds

  • Spread: San Francisco -2.5 (-110) | Seattle +2.5 (-110)
  • Moneyline: San Francisco -140 | Seattle +120
  • Over/Under: Over 45 (-110) | Under 45 (-110)

More NFL picks and odds from Covers


49ers vs Seahawks trend to know

Seattle has covered the 4Q Spread in nine of its last 11 games (+6.75 Units / 47% ROI). Find more NFL betting trends for 49ers vs. Seahawks.

How to watch 49ers vs Seahawks

Location Lumen Field, Seattle, WA
Date Sunday, September 7, 2024
Kickoff 4:05 p.m. ET
TV FOX

49ers vs Seahawks latest injuries

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Kenny Ducey - Covers
Betting Analyst

Kenny Ducey has worked in sports media for more than 10 years and began his journey as a credentialed reporter with Fordham University's WFUV Sports before moving on to Sports Illustrated. There, he wrote about baseball, basketball, and tennis - twice covering the NBA Finals.

He's been in the betting space for seven years, and has established himself as a top expert in MLB and tennis handicapping with brands like Tennis Channel, NBC Sports, and DraftKings. He's also been a frequent guest on betting shows such as MLB's Bettor's Eye and Tennis Bets Live.

Kenny has a knack for identifying underappreciated pitchers and tennis players as moneyline underdogs and credits his unique data analysis and hours of watching sports as the biggest reasons for success through the years. His best advice to bettors? Watch the games, trust your eye, and always question the public narrative.

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