NCCU was chartered in 1909 and opened in 1910 as the National Religious Training School under the leadership of president James E. Shepard. Suffering financial troubles, the school reorganized in 1915 as the National Training School and again in 1923, when it was acquired by the state of North Carolina and was renamed Durham State Normal School.

In 1925, the state redefined the school's mission, turning it into a four-year liberals arts college, the North Carolina College for Negroes (NCC), the first state-supported African-American liberal arts college in the United States. After expanding through the support of the state and local philanthropists (including Benjamin N. Duke), NCC was finally accredited by the Southern Association of Colleges and Schools in 1937.

The college opened its first graduate programs in the 1940's, in law (1940) and library science (1941). In 1947, the college was renamed yet again, this time to North Carolina College at Durham; in the same year, founding president James Shepard died after having headed the school for nearly 40 years.

In 1972, the college, which had been given its current title, North Carolina Central University, in 1969, became part of the 16-member University of North Carolina System.

The NCCU School of Law is currently undergoing a multimillion dollar major renovation of the Turner Law School Building, which is scheduled to be finished in 2005. When finished, the 100,000+ square foot (9,300 m²) building will be one of the largest public law school facilities in the Southeast.