The sophomore partially tore the medial collateral ligament and injured the patella tendon in his right knee Wednesday against Butler. An MRI on Friday confirmed the injury, which is similar to one he had last March.
Creighton spokesman Rob Anderson said the injury could take six months to heal.
Zierden was shooting a team-leading 39.6 percent on 3-pointers and 90 percent on free throws. He was second on the team with 9.5 points a game.