The Office of the College of Arts and Sciences began in 1921 when the North Carolina College for Women reorganized its administrative structure. It was originally known as the Office of the College of Liberal Arts and Sciences with William C. Smith, who was a professor in the English Department, appointed as the first dean. Chancellor Julius Foust was the author of the new structure and he envisioned the College to be the foundation and center of the learning programs at the school. By 1928, 70 percent of the students were candidates for an A.B. degree from the College of Liberal Arts and Sciences.

In 1932, the school became one of the three charter institutions of the Consolidated University of North Carolina and changed its name to Womans's College of the University of North Carolina. As a result of consolidation, the school again reorganized it administrative structure in 1935 to eliminate of the Office of the College of Liberal Arts and Sciences.

There was another university organizational structure change in 1966 which once again established an Office of the College of Arts and Sciences composed of fifteen liberal arts departments. In 1968, Robert L. Miller, a chemistry professor from the University of Illinois-Chicago, was appointed as the dean. He stepped down as dean in 1985 and was replaced by Joanne Creighton of Wayne State University. She left the school in 1990 and was seceded by the then head of the Department of English, Walter Beale. He would serve as dean for the next thirteen years. In 2003 Timothy D. Johnston, a professor of Psychology, was appointed as the dean of the College of Arts and Sciences and still currently holds the position.