49ers at Seahawks NFL Betting Preview – Week 1, September 7, 2025
Game Details:
- When: Sunday, September 7, 2025 at 4:05 PM EDT
- Where: Lumen Field, Seattle
- Spread: 49ers -2.5 Betonline
- Total: 43.5 MyBookie
The NFC West rivalry between the San Francisco 49ers and Seattle Seahawks kicks off the 2025 season Sunday afternoon. The 49ers enter as slight road favorites despite significant roster turnover, while the Seahawks look to end their frustrating home losing streak against their division rivals under the bright lights of a season opener.
Tale of Two Transitions
San Francisco’s Retooling Act
The 49ers are coming off a disappointing 6-11 campaign that ended a three-year playoff streak, but Kyle Shanahan enters his ninth season with championship aspirations intact. The offensive foundation remains strong with quarterback Brock Purdy leading a unit that features Christian McCaffrey, George Kittle, and a supporting cast looking to bounce back from injury-plagued 2024 seasons.
However, the receiver corps presents concerns as Brandon Aiyuk and Deebo Samuel were jettisoned in the offseason, leaving Jauan Jennings as the projected No. 1 option. The defense welcomes back Robert Saleh as coordinator after four years away, bringing his aggressive scheme to a unit anchored by Nick Bosa and Fred Warner.
Seattle’s New Era
The Seahawks enter year two under Mike Macdonald with Sam Darnold taking over at quarterback, replacing the Geno Smith era. Major roster changes include the departures of DK Metcalf and Tyler Lockett at receiver, though Cooper Kupp arrived from the Rams and Jaxon Smith-Njigba is coming off a Pro Bowl campaign.
The defense made a splash addition with DeMarcus Lawrence joining an already impressive unit led by Devon Witherspoon and Leonard Williams, potentially creating “Legion of Boom Part 2.”
Key Matchup Factors
Offensive Line Battle
One of the most interesting storylines centers on Seattle’s offensive line, which has historically struggled but showed improvement during the preseason. Darnold faces the challenge of operating behind a “brutal offensive line” while adjusting to a new system. The 49ers’ pass rush, anchored by Nick Bosa, presents an immediate test for Seattle’s retooled protection schemes.
Defensive Advantages
From Week 9 until the end of last season, the Seahawks ranked fifth in defensive EPA and sixth in defensive success rate, showcasing significant improvement under Macdonald. Meanwhile, San Francisco’s defense struggled, ranking 26th in EPA and 29th in success rate, though Saleh’s return should provide immediate improvement.
Historical Context and Trends
The recent history heavily favors San Francisco in this matchup. The 49ers are 6-1 in their last seven head-to-head meetings and haven’t lost in Seattle since 2021, including a 36-24 victory last season. It’s been four long years since the Seahawks last beat the 49ers at home.
However, Week 1 divisional matchups present unique dynamics. Since 2010, divisional home underdogs in Week 1 have gone 23-7 against the spread, creating a profitable betting trend.
The Betting Analysis
The Case for San Francisco (-2.5)
The 49ers have superior talent and continuity, with Shanahan’s offensive system operating like “a finely tuned machine” when healthy. San Francisco’s depth, talent, and coaching edge provide significant advantages, particularly with their track record of road success in this series.
The offensive ceiling remains elite with McCaffrey healthy and Kittle providing mismatches. Shanahan’s arsenal at full strength gives them a significant edge over Seattle’s work-in-progress offense.
The Case for Seattle (+2.5)
The Seahawks are playing at the notoriously difficult Lumen Field, where crowd noise and emotion factor significantly in season openers. Seattle’s defense has “incredible” potential with Devon Witherspoon and Nick Emmanwori leading a unit that could create problems for San Francisco’s retooled offense.
The roster turnover for both teams, but particularly Seattle’s offensive changes, creates uncertainty that favors the home underdog getting points.
Total Analysis (43.5)
Opening games are rarely clean, with both teams having undergone significant changes, particularly Seattle with new offensive schemes and quarterback. The Seahawks possess a “terrific CB duo” in Witherspoon and Woolen, plus added pass rush with Lawrence, creating defensive advantages.
Historical trends show seven of Seattle’s last eight home openers against NFC opponents have gone under the total, while four of the last five Sunday games at Lumen Field stayed under.
Final Prediction
The combination of Seattle’s defensive improvements, home field advantage, and the profitable trend of divisional home underdogs in Week 1 creates value. With both teams having questionable offensive lines and strong defensive units, the under also presents solid value.
Recommended Bets:
- Seattle Seahawks +2.5 – Take the points with the home underdog in a divisional rivalry where familiarity and emotion often overcome talent gaps.
- Under 43.5 – Two improved defenses and offensive uncertainty point toward a lower-scoring affair than the market suggests.
While San Francisco may have the superior roster on paper, Week 1 divisional games often come down to execution and energy rather than pure talent. The Seahawks’ defensive improvements and home field advantage, combined with the 49ers’ offensive questions, make this spread too generous to pass up.
The pick: Seahawks +2.5 and Under 43.5