Lewis A. Brandon III was born in Asheville, North Carolina, in 1939. As a youth, he was involved with civil rights activities and interracial groups in Asheville, including the Red Cross and the Interracial Youth Council. In 1957, he graduated from Stevens Lee High School and moved to Greensboro to attend North Carolina A&T State University. Following the sit-in of the F. W. Woolworth lunch counter on February 1, 1960, Brandon joined demonstrations against segregated businesses downtown. That same year, he became a member of Greensboro chapters of CORE and NAACP, as well as the Student Executive Committee for Justice, a group formed on the campus of A&T.
Brandon graduated from A&T with a BS degree in 1961. The following year, he participated in voter registration drives, served as vice-president of Greensboro CORE, and was a member of the Greensboro Association of Poor People (GAPP). During this time, he was also part of a group that was arrested on Thanksgiving Day for demonstrating at the S&W Cafeteria in downtown Greensboro. In 1964, he resigned from CORE and joined the United States Army, where he served for two years. In 1966, he returned to Greensboro to seek a MS in biology from A&T. During this time, he again became active in civil rights activities in Greensboro. After graduating with his master’s degree, he taught science at J. C. Price Junior High School from 1968 to 1970. Brandon then joined the staff of GAPP.