In 1840, Reverend Thomas Lawrence of Cincinnati, Ohio organized Payne Chapel A.M.E. Church of Hamilton, Ohio. The organization started with nineteen members. Misters Alfred J. Anderson, Bud Sampson, and Samuel Jones were some of the members present at that time.
This congregation of believers grew rapidly, creating the imminent need for a larger house of worship. The congregation erected a small building in August of 1842. Reverend Owen T. Vickers of Cincinnati, Ohio dedicated the church. Reverend Henry Atkins was the first minister of the congregation. The church became part of the Cincinnati A.M.E. Connection in 1844.

Following the addition to the Cincinnati Connection in the year 1880, the Oxford and Hamilton A.M.E. congregations united and chose to appoint Reverend Jeremiah Lewis as Pastor. In 1880, the congregations separated and Reverend Thomas Knox became Pastor of the Hamilton church. The church stood at the corner of Water (subsequently renamed Monument Avenue) and Ludlow Streets. The city of Hamilton purchased the Monument property in July of 1953 in order to build a parking lot. Under the administration of the late, Reverend Jesse M. Childs, negotiations were completed to purchase a church building, located at 320 South Front Street. In September of 1956, the congregation moved into the church under the Pastorate of Reverend Robert M. Reid.  In October of 1996, the congregation erected a new church building connected to the edifice, at 300 South Front Street, under the auspices of the Reverend Elmer S. Martin.

In November of 2005, The Right Reverend Vaughn Webster assigned Reverend Michael Simmons as Pastor of Payne Chapel. His wife, Reverend Gayle R. Simmons, is the Associate Pastor.