The 49ers (11-1) have won two straight since losing to Miami 77-46 on Dec. 14.
Charlotte led 23-6 in the first 10 minutes and 38-19 at halftime as the 49ers shot 56.7 percent from the field (17 of 30) compared to just 26.7 percent (8 of 30) for the Highlanders.
Radford (5-6) got within 12 points twice, at 57-45 with 7:59 remaining and 62-50 with 3:13 to go, but could get no closer.
Chris Braswell, who came in leading the 49ers in scoring (13.4 points a game) and rebounding (6.9), was held to only five points and three boards.
The 49ers, who are 42-8 all-time against Big South Conference teams, outscored the Highlanders 50-28 in the paint.
Javonte Green's 16 points led Radford.