Kansas City fell to four games behind Cleveland in the hunt for the final AL wild card berth and must also get past the Texas Rangers, who trailed the Tribe by one game after Tuesday's action.
James Paxton (3-0) pitched seven scoreless innings for the Mariners and Justin Smoak stroked a three-run homer for the Mariners.
Paxton turned in a solid performance in his fourth career start. He scattered four hits and struck out 10 while not allowing a walk.
Smoak broke the game open in the fifth inning with a three-run homer that put Seattle ahead 4-0. Kendrys Morales drove in a run in the first inning and finished the night with three hits.
Bruce Chen took the loss for the Royals. He allowed four runs on seven hits and three walks in five innings.