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49ers vs. Seahawks Prediction: Week 5 Odds, Picks & Best Bet

Our 49ers vs. Seahawks prediction for Week 5 includes our best bet, projected score, and the latest odds for Sunday's matchup.

Liam Fox

Last Updated: October 10, 2026 4:30 PM EDT • 2 minute read

San Francisco 49ers tight end George Kittle (85) celebrates after scoring a touchdown as we provide our 49ers vs. Seahawks prediction. — Pictured: San Francisco 49ers tight end George Kittle (85) celebrates as we provide our 49ers vs. Seahawks prediction. Photo by Joe Nicholson via Imagn Images.

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We have an early measuring-stick game for two NFC West powerhouses as I offer my 49ers vs. Seahawks prediction. San Francisco will be looking for revenge Sunday after Seattle bounced its division rival in the playoffs last year.

Kickoff from Lumen Field in Seattle is set for 4:25 p.m. ET (FOX), with the Seahawks priced as a 3.5-point betting favorite.

49ers vs. Seahawks picks & predictions

See all of our experts' NFL picks for Week 5 based on the latest NFL odds.

Pick	Bet size
49ers +3.5 (-125 via FanDuel)	1 unit
Under 46.5 (-115 via bet365)	0.5 units

Total wagered: 1.5 units | Max profit: +1.24 units

49ers vs. Seahawks prediction & best bet

49ers +3.5 (-125 via FanDuel)

The 49ers were stomped in their previous trip to Seattle last January, but both rosters are in very different shape since they last met.

From a 49ers' standpoint, they were missing George Kittle, Trent Williams, and Fred Warner. All three are back in the lineup and once again playing at an All-Pro level in 2026.

Meanwhile, the Seahawks were a runaway train en route to the Super Bowl but are now working through some early-season issues. Seattle lost to the Commanders two weeks ago and nearly left the door open to a Chargers comeback last Sunday.

The 49ers should be able to cover a point spread over a field goal this weekend. FanDuel offers the top price among the best sports betting sites, but there's value betting up to -130.

📡 SBR Edge

The 49ers have won four of their last five games outright in Seattle.

Who is running the ball for Seattle?

This Seattle run game has been decimated since the last time it faced San Francisco. With injuries to Zach Charbonnet and Jadarian Price on top of Kenneth Walker's departure, Emanuel Wilson and George Holani are the top two RBs this week.

That means that even if the Seahawks get out to an early lead, they won't have the ability to grind out long drives and keep the 49ers' offense off the field. That will help San Francisco cover the spread, if not win outright.

Score prediction: Seahawks 23, 49ers 21

49ers vs. Seahawks odds

49ers vs. Seahawks opening odds

Moneyline: 49ers +143 | Seahawks -177
Spread: 49ers +3.5 (-120) | Seahawks -3.5 (+110)
Over/Under: Over 47.5 (-110) | Under 47.5 (-110)

How to watch 49ers vs. Seahawks: Week 5

Date: Sunday, Oct. 11
Kickoff: 4:25 p.m. ET
Location: Lumen Field (Seattle)
TV: FOX

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Written by:
Liam Fox

Liam Fox is a Publishing Editor for Sportsbook Review. Liam spent the past seven-plus years in the sports media industry building his NFL experience and contributing at some of North America's top outlets. His work has appeared on Sportsnet, Forbes, and Complex. He was previously an editor for nearly four years at theScore, specializing in NFL coverage. His career highlights include asking Patrick Mahomes a question at Super Bowl LV media day and shedding light on the champion Philadelphia Eagles' use of analytics through an in-depth interview with their lead data analyst. A graduate of Carleton University's Bachelor of Journalism program, you can usually find Liam writing about sports, watching sports, or playing sports.