Keyshawn Woods added 10 points for the 49ers (12-15, 5-9 Conference USA).
Charlotte shot 53.6 percent in the first half to open a 36-21 lead.
The Golden Eagles (7-19, 2-13) had a 12-6 lead before going 7:27 without a basket. Charlotte had its own issues on offense and only led 16-15 when the drought ended. Then the 49ers reeled off 18 straight points with six different players scoring as the Southern Miss dry spell went 7:39.