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49ers vs. Seahawks prediction, best bet: NFL Week 5 picks, odds, best bets

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Last updated: October 11, 2026 4:41 pm
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Published: October 11, 2026
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Contents
  • 49ers vs. Seahawks prediction, best bet
  • Betting on the NFL?
  • Why Trust New York Post Betting
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The 49ers remain undefeated through four weeks, and what better way to test their mettle than against the reigning Super Bowl champions?

San Francisco’s 4-0 start includes wins over elites such as the Rams and Broncos, while Seattle’s 3-1 mark has come from a softer schedule. 

With three clear-cut Super Bowl contenders, it’s pretty safe to say that the path to a Lombardi Trophy runs through the NFC West, and these divisional games will carry significant weight in the NFL’s hierarchy.

The 12th Man at Lumen Field ostensibly bears more weight than Brock Purdy’s MVP campaign as the Seahawks are 3.5-point favorites. The two split last season’s meetings, while the Seahawks haven’t beaten the 49ers at home in the regular season since 2021.

49ers vs. Seahawks prediction, best bet

San Francisco isn’t without concerns. Nick Bosa remains sidelined, Kyle Juszczyk is doubtful, and Mike Evans is dealing with a rib injury. 

But the 49ers’ garden is still in full bloom: the offense has flourished through the air and on the ground, while the defense has continued to stifle opponents despite these kinds of key injuries. Years of continuity with this veteran core have cultivated a level of leadership and cohesion.


SEATTLE, WASHINGTON - OCTOBER 04: Sam Darnold #14 of the Seattle Seahawks reacts against the Los Angeles Chargers after the game at Lumen Field on October 04, 2026 in Seattle, Washington. (Photo by Steph Chambers/Getty Images)
Sam Darnold #14 of the Seattle Seahawks reacts against the Los Angeles Chargers after the game at Lumen Field on October 04, 2026 in Seattle, Washington. Getty Images

Just how good has Purdy been? His passing attack is averaging an extraordinary 0.48 EPA per attempt, nearly double Baltimore’s second-ranked mark of 0.27. He’s also yet to take a sack this season with Kyle Shanahan’s offense structured around quick decisions and manageable throwing windows.

Defensively, the Seahawks remain impenetrable, leading the NFL in yards allowed. On offense, they’re not quite the crisp operation as we expected — especially without Kenneth Walker. The Seahawks rank 29th in rushing EPA and are without starting running back Jadarian Price, leaving Sam Darnold increasingly dependent on his passing game.


Betting on the NFL?


Darnold’s put up big numbers against Washington with Jaxon Smith-Njigba in Week 3, finishing his return from a glute injury with 379 passing yards and four touchdowns, but he threw two costly interceptions, one of which was a pick-six that handed the lead to Washington with under five minutes left. 

Last week, Seattle needed a muffed punt and Smith-Njigba’s brilliance to separate from the Chargers last week. 

Against a more efficient opponent, relying on those circumstances is a dangerous proposition.

We know this will be a tightly contested battle. So, why take the points when you can grab San Francisco outright for plus money?

THE PLAY: 49ers moneyline (+136, DraftKings)


Why Trust New York Post Betting

Sean Treppedi handicaps the NFL, NHL, MLB and college football for the New York Post. He primarily focuses on picks that reflect market value while tracking trends to mitigate risk.

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