The Tigers (13-10, 9-2 Southwestern Athletic Conference) shot 50 percent from the floor (14 of 28) in the opening half en route to a 34-24 halftime lead.
Jackson State opened it up in the second as the Jaguars (4-19, 3-8) went 5 for 22 from the field (22.7 percent) and 8 of 19 from the free-throw line (42.1 percent).
Southern made only one field goal in the final 9:53 and trailed by as many as 32, 72-40, with 2:16 left to play.
Julius Ingram scored 17 points and had 10 rebounds for the Jaguars, who have lost four straight.
Jenirro Bush added 17 points, Tyrone Hanson had 11 and Phillip Williams 10 for the Tigers, who outrebounded Southern 49-34 and posted a 38-22 scoring edge in the paint.