The San Francisco 49ers arrive in Seattle to begin their 2025 campaign with urgency and high expectations after a frustrating 6–11 season in 2024 that saw them miss the playoffs for the first time since 2020. Much of last year’s struggle came from a devastating rash of injuries to key players including Christian McCaffrey, Nick Bosa, Brandon Aiyuk, and Trent Williams—nearly all of whom are healthy and ready to go for Week 1. The return of Robert Saleh as defensive coordinator has energized the locker room and reinstalled the aggressive, swarming defensive identity that made the Niners a perennial NFC powerhouse in prior seasons. Brock Purdy is back under center after posting over 3,800 passing yards in a season that was efficient but often lacked rhythm due to the rotating door of injured starters. With McCaffrey expected to return to full speed, the 49ers can once again build their offense around his unique dual-threat capabilities, allowing Purdy to operate off play action and find targets like George Kittle and Aiyuk in space. On the outside, the receiving corps is healthy and dangerous, with Deebo Samuel expected to play a more prominent role alongside Aiyuk, giving Purdy a deep and versatile array of weapons. Up front, the offensive line remains anchored by future Hall-of-Famer Trent Williams, though there are still concerns about depth, especially against a Seattle front that loves to generate pressure through the interior.

Defensively, San Francisco enters the season determined to return to its dominant form, with Nick Bosa leading the edge rush and Fred Warner continuing to be the unit’s cerebral leader in the middle. The secondary features Charvarius Ward and emerging young safety Ji’Ayir Brown, giving Saleh plenty of flexibility in disguising coverages and confusing Sam Darnold, Seattle’s new quarterback. While the 49ers struggled against the spread last year at just 5–12, their familiarity with Seattle, especially under head coach Kyle Shanahan, has generally led to solid game plans and execution in this rivalry. San Francisco swept the Seahawks in both meetings in 2022 and 2023 before a slip in late 2024, and the coaching staff will be emphasizing discipline, field position, and mistake-free football to start 2025 the right way. On special teams, rookie kicker Will Reichard will make his debut in the thin margin environment of divisional play, and the team expects to lean on directional punting and coverage units to control the field. With McCaffrey as a bell cow, the defense at full strength, and Purdy operating with more continuity than a year ago, the 49ers are positioned to open the season with a calculated, physical effort. They know that division games carry extra weight in playoff tiebreakers, and a win in Seattle would immediately signal that the Niners are back to contending form. If they execute and avoid early miscues, the 49ers are capable of controlling time of possession, wearing down Seattle’s defense, and walking out of Lumen Field with a key road win and a strong statement.