In July 1871, Vice-Chancellor Charles Todd Quintard nominated The Rev. DuBose to serve as Chaplain of the newly established University of the South and Professor of the School of Moral Science and the Evidences of the Christian Religion. DuBose served as Chaplain of the school from 1871-1883 (he was succeeded by Thomas Frank Gailor). He helped to establish the Theological Department at the university, which would later be known as the School of Theology at the University of the South. A professor in the Theological Department from 1877-1893, DuBose was elected Dean of the Theological Department. He served in that position from 1894 until retiring in 1908. He has been described as possibly the "greatest theologian that the Episcopal Church in the USA has produced."