49ers-Seahawks NFL divisional round playoff preview: Can San Francisco pull off another upset, this time of Seattle?

The Seattle Seahawks and San Francisco 49ers will square off for the second time in a three-week span on Saturday night, though this battle between the two NFC West foes feels different.

The Seahawks are coming off a bye after earning the No. 1 seed in the NFC, and they're now just a single win away from reaching the conference title game for the first time since their Super Bowl run during the 2014 campaign. While not all were dominant by any means, they are on a seven-game win streak and successfully made it through perhaps the toughest division in the NFC.

The 49ers are in a much different position. They snuck past the Philadelphia Eagles last week in the wild-card round, thanks to a go-ahead touchdown to Christian McCaffrey late in the fourth quarter. They are significantly injured, too, and just lost star tight end George Kittle to an Achilles injury. Though a win would keep the 49ers' hopes of playing in a home Super Bowl alive, it's clear these two teams are in very different places entering the NFC West grudge match.

Previous meetings this season

This will be the third matchup between the two teams this season, and the first two were incredibly entertaining. The 49ers edged out a late 17-13 win in Seattle back in Week 1 to open the season, thanks to a game-winning drive from Brock Purdy and then a strip sack turnover by Nick Bosa that sealed the deal near the goal line.

NICK BOSA CALLS GAME

SFvsSEA on FOXhttps://t.co/HkKw7uXVntpic.twitter.com/7cck4psHjo

- NFL (@NFL) September 7, 2025

Then 17 weeks later, the two teams met again in Northern California. Darnold and the Seahawks dominated the entire game to win 13-3 while shutting the 49ers' offense down almost completely. That gave them the No. 1 seed in the NFC, and allowed them to take last week off.

Health update

The 49ers are pretty banged up, and are without Kittle for the rest of the season. Linebacker Fred Warner is trying to return from a fractured and dislocated right ankle, too, but he may not be able to return until the next round should they make it there. LB Dee Winters (ankle), DB Keion White (groin, hamstring), DE Yetur Gross-Matos (knee), LB Luke Gifford (quad) and S Ji'Ayir Brown (hamstring) were all either limited or not practicing due to injuries as of Wednesday, leading to potentially more struggles for their defense.

The Seahawks, coming off their bye, are relatively healthy. Linebacker Demarcus Lawrence is expected to play after being limited with an Achilles injury, too.

The head coaches

It would be a shock if both of these coaches aren't back leading their respective teams next season. Mike Macdonald got the Seahawks to the No. 1 seed in the NFC for the first time in more than a decade in just his second season on the job, so what's not to love there? While there may be time to question Kyle Shanahan soon, he has led the 49ers to the Super Bowl twice and the NFC championship game four times in his nine seasons. He may not have delivered a ring yet, but that's hard to beat.

Key player for the 49ers

The 49ers lost a big target with Kittle now out for the rest of the year, so McCaffrey will have to be an even bigger presence for their offense on Saturday night. And the last time out against the Seahawks, McCaffrey was almost a non-factor. He had just 23 rushing yards, his lowest output of the season.

If he can make some ground up there, and find the end zone at least one, the 49ers will be in a position to pull off the upset.

Key player for the Seahawks

We could pull out one player here, but it's the defense as a unit that will decide this game for Seattle. The Seahawks defense held the 49ers to just 173 yards the last time out, which was the fewest they've had in a regular-season game in the Shanahan era, and allowed only three first downs in the first 30 minutes. They shut McCaffrey down, and didn't allow much at all from Brock Purdy, who has been dealing with plenty of injuries and can be very hit-or-miss.

The 49ers will have undoubtedly learned from their mistakes in Week 18, but a repeat performance now at home on this side of the ball would be huge for the Seahawks' chances.

Betting market watch

"The Seahawks opened as 7.5-point favorites in this game, the fourth time this season that Seattle has been that big a favorite at home; Seattle is 4-0 straight up and 3-1 against the spread in those games. It's also an unfamiliar position for the 49ers, as it's the biggest underdog they've been in the postseason in more than 40 years. We've seen this game twice already this season and San Francisco has scored just 20 total points. I think this game stays under the total of 45.5 points, as Seattle advances to the NFC title game." - Ben Fawkes

Check out more of Ben's work at the Yahoo Sports betting hub.

Prediction

The Seahawks are a 7.5-point favorite at home, and it's no surprise why. They're fully rested and in the midst of a seven-game win streak, and the 49ers have been just scraping by at best the last few weeks. While a third battle between these two division opponents would be fun, the Seahawks should once again control this contest and secure their first spot in the NFC title game in more than a decade.

Seahawks 24, 49ers 10