William served as a Tutor at Baker University (1883–84), then as an Adjunct Professor of ancient languages (1885). He was ordained to the ministry of the M.E. Church in 1886. He then received the appointment of Professor of Greek Language (1887–90), and as President of Baker University (1890–94).
The Rev. Dr. Quayle was appointed Pastor of an M.E. Church in Kansas City, Missouri in 1894. He was appointed to Indianapolis, Indiana in 1897. He was sent back to Kansas City, MO in 1900. He then was appointed Pastor of the St. James M.E. Church in Chicago in 1904, serving there until his election to the episcopacy.
The Rev. Dr. Quayle was elected a delegate to M.E. General Conferences in 1896 and 1908. He was also a Fraternal Delegate to the English Wesleyan Church in 1902.