Video from the game appeared to show a member of the Chiefs’ medical staff popping Mahomes’ kneecap back into position.
The injury occurred in the second quarter as Mahomes picked up a first down by carrying the ball himself.
As the pile of players cleared away after the play, Mahomes was seen tossing his helmet aside and covering his face with both hands, in obvious pain.
A cart was available to take Mahomes off the field but he opted to be helped off by Chiefs personnel instead, the Associated Press reported.
Although Mahomes was later seen walking without assistance, the Chiefs said he would not return to the game, which Kansas City eventually won 30-6.
The Chiefs later said Mahomes would undergo an MRI to determine the extent of the injury.
Seattle Seahawks quarterback Russell Wilson posted a message to Mahomes on Twitter, saying, “Praying for you bro.”
Houston Texans quarterback Deshaun Watson wrote: “Praying my bro @PatrickMahomes is straight!”
Mahomes, 24, a native of Tyler, Texas, who played college football at Texas tech, entered Thursday night’s game already dealing with an ankle injury.
Before leaving the game, the NFL’s reigning MVP had 10 pass completions on 11 attempts for 76 yards.
Mahomes has thrown 15 touchdown passes and one interception this season.
He was replaced by Matt Moore, 35, who was signed by the Chiefs on Aug. 27 after an injury to Chad Henne.
The Associated Press contributed to this story.