Coach Jim Boeheim said the 6-foot-9, 280-pound sophomore will have surgery.
"This is a tremendous disappointment, especially considering the amount of hard work DaJuan has been putting in with our basketball team," Boeheim said in a release issued by the school. "We will certainly miss his contributions."
Syracuse is ranked second in the country and one of three unbeaten teams remaining -- along with top-ranked Arizona and No. 5 Wichita State. The Orange play Miami on the road Saturday.
Coleman started the first 12 games of the season and is the team's best low-post threat. He battled knee issues last season as a freshman and has played just nine minutes since Dec. 20 due to nagging knee problems.
Sources told ESPN.com that the medical staff has tried several options in an effort to get Coleman healthy. However, the Syracuse native remained in significant pain and decided recently to shut it down.
The loss of Coleman is significant for a team that has been searching for more production and consistency from its bench. Without Coleman in the lineup Saturday, the Orange were outrebounded 35-24 in a close win over Pittsburgh.
Boeheim could elect to give increased minutes to defensive-minded big men Rakeem Christmas and Baye-Moussa Keita. He also may elect to use 6-8 freshman Tyler Roberson, who has played sporadically this season.