Wilson completed 15-of-21 passes for 171 yards with an interception and also ran the ball six times for 29 yards for the Seahawks (10-5), who hold one of the NFC's two wild card positions.
Marshawn Lynch piled up 111 yards on 26 carries with a score and also caught a TD pass. Doug Baldwin made two scoring grabs among his four catches for 43 yards.
The Seahawks have amassed 150 points in three straight wins over Chicago, Arizona and San Francisco.
Colin Kaepernick went 19-of-36 for 244 passing yards, a touchdown and an interception for the NFC West-leading 49ers (10-4-1).
Swim Week Miami Beach 2014 [PHOTOS]