The school announced Thursday that Harris, who led Wake with 608 rushing yards last season, is ineligible for his senior season. The school also said it has asked the NCAA for a waiver to restore his eligibility.
Citing school policies on student privacy, an athletic department spokesman told The Associated Press he is unable to say whether Harris' ineligibility is related to academics.
Wake has dealt with Harris' absence before -- he missed one game last season and four in 2011 with injuries.
The likely new starter is DeAndre Martin (6-foot-2, 235 pounds), a physical runner who rushed for 484 yards as a redshirt freshman last fall. Martin, recruited by some schools out of high school in Miami as a safety, has gained almost 50 pounds since signing with the Demon Deacons in February 2011.
But depth becomes a huge concern without Harris: No other tailback on the roster has a college carry.