Wilkins, a redshirt junior, rushed for 379 yards and four touchdowns last season. He was expected to be a "co-starter" this season.
According to the news release, Wilkins failed to meet the NCAA standards for progress toward a degree.
"An appeal was filed with the NCAA for Jordan's reinstatement based on an administrative error but was denied this week," the school's release said. "The athletics department takes full responsibility and holds itself accountable when situations like this occur with our student-athletes. We will support Jordan to the fullest during this time and look forward to seeing him return to the field."
Ole Miss, which ranked seventh in the league in rushing and lost Jaylen Walton to graduation, will now be without its top two rushers from last season.
In Wilkins' absence, Ole Miss will likely lean more heavily on Akeem Judd, a 5-foot-11, 228-pound senior who played in every game last season. Judd finished third on the team with 421 rushing yards and tied for fourth with three rushing touchdowns.
Eric Swinney, a redshirt freshman and former four-star recruit, is also expected to contribute at running back.