Alfonzo Houston scored 13 points for top-seeded NCCU (26-5), while Jay Copeland netted 11.
For eighth-seeded Howard (8-25), James Daniel was the lone player in double figures with 15 points.
NCCU came out firing in the first half by shooting a blistering 71.4 percent from the field and running out to a 47-23 lead at intermission. Howard, meanwhile, shot only 21.7 percent in the opening 20 minutes.
The Eagles cooled to 53.6 percent field goal shooting after halftime but still cruised to the dominating 46-point victory.
NCCU shot 10-of-20 from 3-point range and forced Howard into 16 turnovers.
The Eagles will play either Savannah State or Norfolk State in the semifinals on Friday.