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 in the first half against Florida State. He landed awkwardly trying to catch a high pass in transition and could put little pressure on his leg. 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.