Harrison was born in Savannah, Georgia, and attended the preparatory school of Emory College. In 1850, he became an itinerant minister of the Methodist Episcopal Church, South. In 1859, he was appointed to the faculty of the East Alabama Male College in Auburn, Alabama as Adjunct Professor of Languages, and from 1861 through 1862 was president of the Auburn Female College, today Auburn High School. He returned to Emory, receiving the Doctor of Divinity degree in 1866. Later that year, Harrison became pastor of the First Methodist Church in Atlanta, Georgia, the first of four terms as pastor there, the last of which ended in 1877.