NFL Week 1: 49ers vs. Seahawks Storylines, Picks & Best Bets

Updated
We may use AI tools to support content creation and editing. While we aim for accuracy via strict editorial standards, readers should independently verify important information. Ads on our site are served by Google AdSense and are not controlled or influenced by our editorial team.
49ers' Brock Purdy sets up to throw.

The NFC West rivalry will write another chapter when the San Francisco 49ers play the Seattle Seahawks. Here are the storylines, picks, and best bets for the NFL Week 1 game between the 49ers and Seahawks.

49ers vs. Seahawks: Game Information

  • 🏈 Game: 49ers vs. Seahawks
  • 🕗 Time: 4:05 p.m. ET
  • 🏟 Location: Lumen Field — Seattle, Washington
  • 📺 TV Channel: FOX
  • 💻 Live Stream: FOX One

Top Storyline: Sam Darnold Era Begins In Seattle

After trading Geno Smith to the Las Vegas Raiders, the Seattle Seahawks signed Sam Darnold to a three-year, $100.5 million contract.

If things go south, the Seahawks could get rid of Darnold after one year. That’s the worst-case scenario.

However, Seattle is hoping to get the Darnold who threw for 4,319 yards and 35 touchdowns as the quarterback of the Minnesota Vikings.

Darnold completely revitalized his career in 2024 by leading Minnesota to a 14-3 record and a playoff appearance.

How much of Darnold’s success can be attributed to Vikings coach Kevin O’Connell? That question will be answered by the end of this season.

49ers vs. Seahawks: Picks and Best Bets

49ers -2.5 (-106)

Last year was the season from hell for the 49ers.

Brock Purdy, Christian McCaffrey, George Kittle, Brandon Aiyuk, and Trent Williams all missed time in 2025. Every one of those players besides Aiyuk is healthy and ready to play on Sunday.

Receiver depth could be a problem for the 49ers. Aiyuk is out for the foreseeable future. Jauan Jennings will likely suit up, but he’s been dealing with a calf injury. Expect Ricky Pearsall to see an increased role in production.

Speaking of receivers, Seattle moved on from DK Metcalf and Tyler Lockett this offseason. Jaxon Smith-Njigba is now the No. 1 option, with Cooper Kupp from the Rams as his No. 2.

Picking against the home underdog in a division matchup feels like a sin. However, the 49ers have more answers than questions. If healthy, San Francisco can win 10 games because of their favorable schedule.

Darnold is still a wild card. I’ll take the 49ers to pull away late for the victory and cover.

Christian McCaffrey Over 72.5 Rushing Yards (+155)

If there’s anyone who wants to prove they can return to form, it’s Christian McCaffrey.

Two seasons ago, McCaffrey was the best offensive player in the NFL. Two seasons ago, McCaffrey rushed for over 72.5 rushing yards in 14 games, including the postseason.

McCaffrey has never rushed for less than 79 yards against the Seahawks (6 games). CMC has a big day in Week 1.