Last Updated on September 6, 2025 9:20 pm by Anthony Rome
In this 49ers vs Seahawks prediction, bettors get a heated NFC West rivalry where physicality and defense usually set the tone. San Francisco comes in as a slight road favorite with Brock Purdy directing Kyle Shanahan’s offense and Christian McCaffrey as the engine. Seattle, meanwhile, will counter with Geno Smith, DK Metcalf, and Kenneth Walker III in a hostile Lumen Field environment. With the spread at just a point, this game has coin-flip potential.
49ers vs. Seahawks Event Information
- Matchup: San Francisco 49ers at Seattle Seahawks
- Date: Sunday, September 7, 2025
- Time: 4:25 p.m. ET
- Stadium: Lumen Field — Seattle, WA
- TV: FOX
49ers vs Seahawks Betting Odds
Odds via Bovada:
- Spread: 49ers -1
- Moneyline: 49ers -115 / Seahawks -105
- Total (O/U): 43.5
Public betting splits can be tracked at The Spread’s NFL public betting chart. Current action shows bettors leaning slightly toward San Francisco on the spread, while totals betting is split with a small push toward the under.
49ers’ Offense vs. Seahawks’ Defense
The 49ers’ offense runs through Christian McCaffrey, who remains a nightmare as both a runner and receiver. Brock Purdy thrives in Shanahan’s scheme by staying efficient and distributing to Deebo Samuel and Brandon Aiyuk on crossers and quick hitters.
Seattle’s defense, led by Devon Witherspoon and Riq Woolen in the secondary, matches up better than most with San Francisco’s skill talent. The question is whether their front can handle McCaffrey without overcommitting and leaving Purdy clean play-action looks.
Seahawks’ Offense vs. 49ers’ Defense
Geno Smith is steady and efficient, but this matchup is his toughest. The 49ers’ pass rush, led by Nick Bosa, is capable of wrecking drives by forcing Seattle behind the chains. Seattle’s run game with Kenneth Walker III must be effective early to keep Geno from facing long third downs.
San Francisco’s linebackers, especially Fred Warner, give them the ability to cover tight ends and backs, forcing Geno to take more shots outside. That puts pressure on DK Metcalf and Tyler Lockett to win contested matchups against an elite secondary.
Key Matchups to Watch
- McCaffrey vs. Seahawks’ linebackers – If he dominates in space, Seattle will be playing from behind.
- Nick Bosa vs. Seattle’s O-line – Can the Seahawks’ tackles survive Bosa’s relentless edge pressure?
- DK Metcalf vs. Charvarius Ward – Metcalf’s physicality against Ward could tilt third-down situations.
- Third-down efficiency – Sustained drives will be critical with two defenses capable of forcing punts.
49ers vs Seahawks Prediction
Divisional games are always tricky, especially in Seattle, but the 49ers’ defensive front gives them the edge in the trenches. Purdy doesn’t need to win this game alone — McCaffrey and the short passing game will wear down the Seahawks late. Expect a close, physical contest where San Francisco escapes with a narrow win and cover.
Best Bets:
- 49ers -1
- Under 43.5
Projected Score: 49ers 23, Seahawks 20