Russell Wilson's 35-yard touchdown pass on fourth down ensured the Seahawks clinched the NFC Championship title on Sunday to reach the Super Bowl for just the second time in their history.
They will be hoping to make it second time lucky, after losing against Pittsburgh in 2005 first time around, when they face the Broncos, who earlier defeated the New England Patriots, at the MetLife Stadium on February 2.
The 49ers were leading 17-10 towards the end of the third quarter when Steven Hauschka's 40-yard field goal made it a four-point game ahead of the final period.
San Francisco were then made to pay for an offside infraction, which left Wilson with a free play.
He picked out Jermaine Kearse, who took a fine catch in the end zone before Hauschka kicked his third field goal to put the Seahawks within touching distance of the Super Bowl.
However, it was San Francisco that had possession deep in opposition territory in the closing stages to set up a tense finale.
But when Richard Sherman crucially intercepted Colin Kaepernick's pass to Malcolm Smith with just 22 seconds left, the chance was gone as the Seattle players started to celebrate.