The visiting Cardinals (7-1) came up with 18 steals, three blocked shots, and out-rebounded the Cougars (5-3) 35-28 en route to their fifth double-digit win of the season.
Blackshear was one of four Louisville players in double figures. The Cardinals shot 45.3 percent from the field to the Cougars 34.8 percent.
Adjehi Baru led College of Charleston with 16 points and 14 rebounds. The Cougars had a four-game winning streak snuffed out.
Louisville was in control the entire way, leading at halftime 36-16.