Coach Tom Matukewicz announced the injury Tuesday, three days after the senior played sparingly in the second half of a 29-28 loss at Indiana State. Jackson, the Redhawks' leading rusher each of the past two seasons, gained 265 yards on 56 carries in three games this year.
His 186 yards in a 27-24 win over Southern Illinois on Sept. 12 were a career-high.
"Obviously, it's disappointing," Matukewicz said. "You work really hard as a student-athlete and dream about your senior year. This is how life works sometimes. DeMichael plans on taking a medical redshirt and returning to finish his career at Southeast next year."
Jackson, who has rushed for 1,996 yards and averaged 5.4 per carry with nine touchdowns in his career, will undergo surgery Monday.
SEMO (1-2) hosts Division II Shorter University on Saturday.