For a short time he taught at district schools, but interest in the ministry led him to begin studying theology with Rev.

His preaching style, according to his parishioners, was appealing, enlightening, and spiritually uplifting, and his popularity led to ever-increasing church attendance.

Nevertheless, many of his sermons were collected in his works The Balance; or, Moral Arguments for Universalism (1847) and Graces and Powers of the Christian Life (1853).

This appointment was less fruitful than he expected, and in 1856 he relocated to Albany, New York, where he ministered at the Division Street Unitarian Church until 1863.

He retained his position in Springfield until 1880, when he resigned from active ministerial duties and devoted more time to writing and lecturing.

He had also served as a leader of the Christian Amendment movement, which advocated a provision in the United States Constitution affirming the right to teach the Bible in public school.

Since most of his lecturing and counseling were provided gratis, Mayo was forced at first to depend on an annual grant from the American Unitarian Association and later on contributions from friends and well-wishers.

At the request of Dr. William T. Harris, U.S. commissioner of education, Mayo dedicated himself to writing the history of American common schools.