In 1863, St. James Society, or Station, was organized by Rev. Winston, Rev. Burks, Prog. Samuel Newton, and Jesse Stanton. The Society met in the building across the street from its current location on North St. in Cape Girardeau. For the next three years Rev. Kirkman, Rev. James Madison, and Rev. George Gains served this Station.
In 1867, St. James Society became St. James A.M.E. Church. In 1875, under the leadership of Rev. Spotswood Rice, the current facility was erected. St. James is the oldest African-American church in the city of Cape Girardeau and has served the community in numerous ways under God-sent leadership.
St. James was placed on the National Register of Historic Places by the United States Department of the Interior in 2014.