On April 16, 1885, a Baptist mission of Coliseum Baptist Church was begun in unused servants' quarters of the corner of Maple and Cherokee Streets. On November 16, 1898, twenty-six charter members created the Carrollton Baptist Church.

In 1901, the city of Carrollton was annexed by the city of New Orleans. The small congregation of Carrollton Baptist Church purchased property on the corner of St. Charles Avenue and Hillary Street and changed the church name to Saint Charles Avenue Baptist Church. The lot on the corner of St. Charles Avenue and Audubon Street was purchased in 1924, and in 1926 the church moved to its present location.

Throughout its history, the church proved instrumental in the development of the New Orleans Baptist Theological Seminary, the Southern Baptist hospital and every other Baptist Home Mission agency in New Orleans. Indeed, the church has always fostered a strong emphasis and interest in both home and foreign missions. Over fifty foreign missionaries have been members of Saint Charles Avenue Baptist Church.

Despite its relatively small size, Saint Charles Avenue Baptist Church is known and respected throughout Baptist life for its innovative ideas and creative leadership. For example, the church has always invited women to fill important leadership positions. In 1971, Saint Charles Avenue Baptist Church became the first Baptist church in Louisiana to ordain women as deacons. In 1980, the church became the first Baptist church in Louisiana to ordain a woman to the Gospel ministry.

Striving to be a prophetic voice of faith in New Orleans and beyond, Saint Charles Avenue Baptist Church works to build and maintain an attitude of openness and a spirit of acceptance, affirming and living out true Baptist ideals. In a business session, held Sunday, May 27, 2001, Saint Charles Avenue Baptist Church considered, voted on and accepted the decision to end affiliation with the Southern Baptist Convention.