The win hands Seattle a first-round playoff bye, and home-field advantage in the post-season knockout rounds leading to next month's NFL championship spectacle.
"Our defense picked us up. They have been all year. They've been doing a great job," said quarterback Darnold.
The Seahawks yielded only 53 rushing yards against a highly rated 49ers offense, while Seattle's Kenneth Walker III personally rushed for 97 yards to help secure the NFC West division title.
"Incredible," Walker said. "We worked so hard from day one... we've been grinding up till now. But we got a lot of work to do, so we can't get satisfied."
For the 49ers, the loss means hitting the road for next weekend's wild-card round, and a trickier route to Super Bowl LX, which is being held at their home stadium in Santa Clara, California, on February 8.
With so much at stake, and both teams arriving at the regular season's final weekend on six-game winning streaks, a fiercely contested clash was assured - but Seattle started far more explosively.
Zach Charbonnet ran for a 27-yard touchdown, Darnold peppered pinpoint throws, and a swarming Seahawks defense did not give up a first down in the first quarter.
Seattle's early dominance was not fully reflected in the 10-3 half-time score.
Quarterback Brock Purdy's 49ers offense appeared to finally cut loose in the fourth quarter.
But an eight-play drive collapsed yards from the end zone, with an interception deflected off Christian McCaffrey.
As the clock ticked down, a worn-out and injury-depleted San Francisco defense struggled to cope with Seahawks' rapid rushing game, led by Walker and Charbonnet.
Seattle kicker Jason Myers missed a 26-yard field goal late on - his second miss of a windy night - but the Seahawks were not made to rue his profligacy.