Coach Jim Boeheim says McCullough suffered a torn anterior cruciate ligament in his right knee and will miss the remainder of the season.
McCullough injured the knee Sunday night against Florida State, laning awkwardly trying to catch a high pass in transition. He was helped to the locker room and never returned. Surgery has not yet been scheduled.
The 6-foot-10 McCullough was averaging 9.3 points, 6.9 rebounds and 2.1 blocks and had started all 16 games.
Boeheim said sophomore Tyler Roberson would assume McCullough's spot in the starting lineup.