49ers vs. Seahawks Final Score Prediction for NFL Week 1 (San Francisco’s Balance Gives Edge in Seattle)

Sean Treppedi | Sep 5, 2025

San Francisco’s offensive balance and defensive pressure make them the sharper side in a tight Week 1 divisional matchup at Seattle. / Kyle Terada-Imagn Images

San Francisco kicks off 2025 trying to erase the memory of an injury-riddled 2024 campaign, but despite those woes, their underlying efficiency metrics still ranked among the NFL’s best. 

Seattle begins year two under Mike Macdonald with a retooled offense led by Sam Darnold and bolstered by the addition of Cooper Kupp, though the defensive core is still the unit’s identity. 

The Seahawks have lost six of its last seven to San Francisco, but the Seahawks’ defensive upgrades and Lumen Field’s hostile environment make this the 49ers’ toughest divisional opener in years.

These two haven’t shared a losing season in the same year since 2018, so with a 1.5-point spread, there’s little ground to be yielded from the get-go.

49ers vs. Seahawks Odds, Spread and Total

Odds via FanDuel Sportsbook

Spread

• 49ers -1.5 (-110)
• Seahawks +1.5 (-110)

Moneyline

• 49ers (-126)
• Seahawks (+108)

Total

• Over 43.5 (-104)
• Under 43.5 (-118)

49ers vs. Seahawks How to Watch

• Date: Sunday, September 7, 2025
• Time: 4:05 p.m. ET
• Venue: Lumen Field
• How to Watch (TV): Fox Sports
• 49ers Record: 0-0
• Seahawks Record: 0-0

49ers vs. Seahawks Final Score Prediction

This line has moved in Seattle’s direction since opening, but San Francisco laying a point and a half on the road says there’s skepticism around Darnold and the new-look Seahawks. This is still primarily a 49ers group that was in the Super Bowl two years ago. Their offense was still elite — when healthy — last season, ranking top three in yards per play and producing explosive passes on 14 percent of attempts — the highest rate in the league. Christian McCaffrey’s dual-threat production also spells problems for a Seahawks defense that allowed the third-most yards per reception to running backs in 2024. 

Seattle’s rushing tandem of Kenneth Walker III and Zach Charbonnet must produce, but San Francisco’s front ranked second-best in the league allowing just 19.2 carries per touchdown. The Seahawks also enter with questions in red-zone execution, ranking near the bottom of the NFL in first-quarter efficiency last year.

While Seattle’s defense is talented and Lumen Field remains one of the NFL’s most difficult places to play, San Francisco has the advantage in offensive versatility and defensive pressure metrics (28% completion allowed under pressure). In a game that projects close, the team with fewer schematic weaknesses and more ways to win situational downs deserves the lean.

Final score prediction: 49ers 24, Seahawks 20

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Odds refresh periodically and are subject to change.

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