Commission membership as established in the 1971 act consisted of 12 North Carolinians of Indian ancestry commissioned by the governor following selection by their tribal communities. Certain state officials also served as ex officio members. During its early years, the commission operated as an independent agency, with its budget and personnel matters being handled generally by the Department of Administration. In 1977 the state legislature reformed the commission and formally transferred it to the Department of Administration, placing it under the direction and supervision of the department's assistant secretary for advocacy programs. By the early 2000s the commission consisted of 19 representatives of the Indian community, 2 persons appointed by the General Assembly, the secretary of health and human services, the director of the State Employment Security Commission, the secretaries of the Department of Administration and the Department of Environment and Natural Resources, and the commissioner of labor.
At times friction has developed between a particular tribe and the Commission of Indian Affairs. For example, in August 2001 the North Carolina Court of Appeals overturned the recommended decision of an administrative law judge in 1999 that the Occaneechi had met the criteria to be recognized by the state as an Indian tribe. In September 2001 the commission decided that it was not ready to accept the tribe into its fold and asked the North Carolina Supreme Court to consider hearing the case. This case was later decided in favor of the Occaneechi, who officially became the Occaneechi Band of Saponi Nation. Other tribes and Indian organizations represented on the Commission of Indian Affairs are the Eastern Band of Cherokee Indians, the Coharie, the Haliwa-Saponi, the Guilford Native American Association, the Lumbee, the Meherrin, the Waccamaw-Siouan tribe, the Triangle Native American Society, the Sappony, the Cumberland County Association for Indian People, and the Metrolina Native American Association.