King suffered a torn meniscus in his right knee in Thursday's 48-17 drubbing of Tulane. The injury occurred on a handoff in the second quarter.
Houston coach Major Applewhite and his staff were taken aback by the injury. King was hurt on a non-contact play and had to be carted to the locker room after limping to the sideline.
"He simply handed the ball off and went to carry out his fate," Applewhite told reporters, per the Houston Chronicle. "It all kind of stunned us, quite honestly, when he said he could not straighten his leg out."
King was in the midst of a superb season for the Cougars, who are sitting atop the American Athletic Conference West Division with an 8-3 overall record and 5-2 mark in league play.
The dual-threat junior amassed an FBS-leading 50 touchdowns in 11 games, throwing for 2,982 yards and 36 touchdowns while rushing for 674 yards and six scores. King had only six interceptions.
True freshman Clayton Tune is expected to take over the starting job. Houston will face Memphis on Nov. 23 in a game that will decide the AAC West title and a spot in the conference championship game.
Tune came on in relief of King in Thursday's rout of Tulane and finished 6 of 15 for 108 yards with a pair of touchdowns and one interception.