Wilson completed 18-of-29 passes for 271 yards, three scores and zero interceptions, while rushing for 57 yards on eight carries. Mahomes -- an MVP candidate -- completed 23-of-40 passes for 273 yards, three scores and no interceptions. He had 33 yards on the ground.
Seattle earned an NFC playoff spot with the victory.
"What a huge night for Seahawks fans and 12s and all that are concerned," Seahawks coach Pete Carroll told reporters. "It was a great night and challenge because they are such a great team. The coaching and everything they've got going on. The whole year they have put together."
The Seahawks drew first blood, getting the first of Chris Carson's two touchdowns on the night on their opening drive. Seattle built a 14-10 lead at halftime, but Mahomes led the Chiefs back.
Seattle began the third quarter with a field goal on its opening drive. Mahomes followed suit by orchestrating a 7-play, 83-yard drive. He capped off the drive with a 25-yard touchdown pass to Charcandrick West, tying the score at 17-17.
Wilson responded with an 8-play, 80-yard scoring drive. He iced that drive with a 27-yard touchdown pass to Doug Baldwin.
The teams exchanged punts on the next two drives before Kansas City got a 29-yard field goal from Harrison Butker with 10:32 remaining, making the score 24-20 with Seattle in the lead.
But Wilson answered yet again, throwing a 2-yard touchdown pass to Ed Dickson to cap off a six-play, 68-yard drive. Mahomes answered with another long scoring drive, cutting into the deficit. The second-year gunslinger rushed for a two-point conversion following the score, getting the Chiefs to within three points of the Seahawks.
But Seattle put the game on ice with a 75-yard scoring drive on the following possession. The Chiefs could only muster another field goal, as the Seattle defense held up down the stretch.
Carson had 116 yards and two scores on 27 carries for the Seahawks. Baldwin paced Seattle's pass-catchers with 126 yards and a score on seven catches. Damien Williams had 103 yards on 13 carries for the Chiefs.
"This year has been special," Wilson said. "I think we really came together. One of my favorite parts of this season has been watching guys celebrate with one another ... the little things and really enjoying everyday. You don't take that for granted. For us it has been a really special year."
Sunday's loss marked the first time this season that the Chiefs have suffered back-to-back defeats. The Chiefs host the Oakland Raiders at 1 p.m. on Sunday at Arrowhead Stadium in Kansas City. The Seahawks host the Arizona Cardinals at 4:25 p.m. on Sunday at CenturyLink Field in Seattle.
"We've been in every game we've lost but we have to find ways to win," Mahomes said. "As we go into this next week against the Raiders, they are going to be ready to play us so we gotta find a way to win ... You have to find a way to win these games and we haven't been lately. That's the most frustrating thing."