The balance of power in the A.F.C. might have shifted Thursday night on a quarterback sneak.

Kansas City’s Patrick Mahomes, the reigning winner of the N.F.L.’s Most Valuable Player Award, sustained what appeared to be a serious right knee injury after surging for a first down in the second quarter of the Chiefs’ game on Thursday night at Denver. After being tended to by trainers, he limped off the field and, within minutes, was ruled out for the remainder of the game.

The knee injury comes as Mahomes, 24, has been battling a left ankle injury he sustained in the season opener and aggravated in Sunday’s loss to the Houston Texans.

The Chiefs, who began Thursday with a half-game lead in the A.F.C. West over second-place Oakland, did not immediately offer additional information on Mahomes’s status. Matt Moore, who had played only nine snaps since 2017, replaced Mahomes and led the Chiefs (5-2) to a 30-6 win over the Broncos (2-5).