Thursday and Friday night football served as the appetizer for a loaded Week 1 NFL slate. On Sunday, the 2025 season truly kicks off with games aplenty, and in the afternoon window we’re treated to an NFC West showdown as the Seattle Seahawks host the San Francisco 49ers. The stakes are already high for this rivalry game, so put your afternoon nap on hold and tune in.
Get all the details for this matchup with a Seahawks vs. 49ers prediction and pick on DraftKings Sportsbook for this Week 1 action.
Seahawks vs. 49ers prediction, preview
San Francisco 49ers
After a disastrous 2024 that saw the 49ers finish just 6-11 at the bottom of the NFC West, this tea, returns under Kyle Shanahan with their eyes on the price of a division title… and playoff run.
Key pieces of the offense return with Brock Purdy having signed a massive extension over the offseason, George Kittle at tight end, and Christian McCaffrey at halfback. The receiver corps does look somewhat depleted as Brandon Aiyuk keeps rehabbing a serious knee injury suffered last season, but that positions Ricky Pearsall well for a second-year breakout alongside Jauan Jennings on the outside. The defense should also have an opportunity to rebound with EDGE Nick Bosa, linebacker Fred Warner and the addition of Mykel Williams in the first round of the 2025 NFL Draft along with other defenders in the next three rounds, however, the loss of Talanoa Hufanga does hurt in the secondary.
Personnel-wise, the 49ers have plenty of talent in place along with one of the top coaches in the game as long as Kyle Shanahan remains in charge. The offense was respectable last season despite injuries to McCaffrey and Aiyuk, and Kliff Kubiak now takes over as coordinator on that side of the ball with prior experience on this staff. The passing game should thrive and see targets largely condensed into just a couple of targets, but a late-week calf injury to McCaffrey looms large and creates a massive X-factor with his questionable tag. If he can’t go, new 49er Brian Robinson will step in as the primary halfback for his first action with the team.
Seattle Seahawks
On the opposite sideline are the Seattle Seahawks, who underwent some fairly significant changes over the offseason following a 10-7 2024 campaign in which the team barely missed out on a playoff berth.
Seattle fired offensive coordinator Ryan Grubb and replaced him with Klint Kubiak, who sees the opportunity to coach against his brother in this spot. The new-look offense seems to have been built in the new coach’s image as they’re set to emphasize a zone-run scheme with new faces at quarterback and wide receiver. The Seahawks parted ways with Geno Smith and DK Metcalf via trade and replaced the pair with Sam Darnold and Cooper Kupp, the former of whom excelled with solid coaching last year but raises questions of whether he can keep the magic of a near-MVP season rolling, and the latter sees concerns about Father Time taking a toll on his abilities. However, they’ll play alongside Jaxon Smith-Njigba, a breakout star of 2024, as well as Kenneth Walker and Zach Charbonnet, one of the league’s best halfback duos.
The offense may have taken gambles in Darnold and Kupp, but one can see the vision of a great unit if all works out. The Seahawks’ defense may become their calling card, though, especially with a pair of talented cornerbacks in Devon Witherspoon and Tariq Woolen now joined by second-round safety Nick Emmanwori. Julian Love is another excellent safety, so this secondary looks fierce. With Leonard Williams and DeMarcus Lawrence on the edge and Byron Murphy projected to take a leap in year two, this defense has the makings of a truly elite unit.
Seahawks vs. 49ers pick, best bet
DraftKings Sportsbook lists the 49ers as1.5-point favorites and -122 favorites on the Moneyline. The Seahawks are listed at +102 on the Moneyline with the game total set at 43.5 combined points.
This game looks like it can become a very interesting spot for a chess match between these division rivals. While Seattle played a very pass-happy style last season, that should scale back at least slightly this season in Klint Kubiak’s offense and there’s been talk that Zach Charbonnet will see much more work to supplement Kenneth Walker and keep the latter back fresh (and hopefully, healthy). Walker in particular excels in zone run schemes and the Niners weren’t great at stopping the run last season, so he could gash this defense if the multiple draft picks San Francisco made in their front seven aren’t yet up to speed. However, it’s clear that limiting the run would be a focus this year.
Additionally, this brings the first test for Sam Darnold in a Seahawks uniform. Kubiak wants to run a West Coast offense in a somewhat similar system to what the Shanahan coaching tree uses, including the Vikings’ scheme that Darnold excelled under last year alongside Kevin O’Connell. He doesn’t have the same caliber of weapons on offense, but if the run game can insulate the quarterback, he may be able to do some damage. However, the 49ers’ defense still sees the benefit of great coaching and defensive coordinator Robert Saleh is no slouch — again, this will truly test the Seattle offense.
Much of the outcome here hinges on Christian McCaffrey’s health. While the halfback said he feels great and believes people may be overreacting slightly to his new calf injury, it’s still a cause for concern. His injury history is rather extensive, but if the star actually does play through the calf ailment without issue, he certainly adds a dynamic element to an offense in need of playmakers. However, it’s tough to predict exactly what his workload looks like to open the campaign, especially after he went from a full practice participant on Wednesday to limited on Thursday, then a DNP on Friday. Kittle will see plenty of receiving work and Pearsall’s poised for a breakout, but I actually like the Seahawks to keep things close and escape with a win at home here on the backs of their run game.
