The score was tied at 35 at intermission and USC-Upstate pulled away on an 11-2 run with 16:19 to go. The Norse got no closer than four points for the rest of the game and USC-Upstate held its largest lead at 11.
The Spartans shot 53.1 percent from the floor, but made just two 3-pointers on 11 attempts.
Tyler White scored 17 points to lead Northern Kentucky (7-10, 3-2). The Norse shot 12 of 15 (80 percent) from the free-throw line and made seven from 3-point range.
DeSean Murray, who averaged 20.2 points as a sophomore at Presbyterian, will transfer to Auburn to play for coach Bruce Pearl.
Former Kentucky guard Ed Davender, the only Wildcat with at least 1,500 points and 400 assists, has died. He was 49.