First African Presbyterian Church, founded in 1807, was the first Black Presbyterian congregation in the United States. In 1809, First African became a chartered organization. Many of its pastors have been central figures in the history of Black Presbyterians.

John Gloucester, a slave and noted preacher born in Tennessee in 1776, arrived in Philadelphia in 1807. His appearance coincided with the search by the Evangelical Society of Philadelphia for a Black pastor to lead the Black Presbyterian congregation for which it was trying to collect sufficient funds to build a church. While waiting for his freedom and for the funds to materialize, Gloucester began to gather a congregation and to preach in a house on Gaskill Street. His congregation quickly grew too large for the house and he moved it outdoors to the corner of 7th and Shippen (now Bainbridge) Streets, where the First African Presbyterian Church was built and dedicated in May of 1811. Gloucester preached his first official sermons to a congregation of 123 people, including Cato Freeman, James Prosser, Jacob Craig, and Quommany Clarkson. Gloucester served the church until his death in 1822. John Gardner and various supply ministers succeeded him.

In 1859, the congregation called the Rev. Jonathan C. Gibbs. He remained pastor until 1865. R. B. Johns succeeded Gibbs, leaving First African in 1879.

In 1879, the congregation met and agreed to move to a more convenient location. The building at 7th and Shippen was sold and until 1891 services were held in temporary spaces at 16th and Lombard Streets. In the early 1890s, the congregation moved to its new house of worship at 17th and Fitzwater Streets.

From the departure of Johns until 1900, First African was served by a succession of short-term pastors. At that time a call was extended to the Rev. John W. Lee, who remained with First African until 1917. In addition to fulfilling his pastoral responsibilities, he conducted a tent ministry in South Philadelphia and began the first vacation Bible school for Black children. In 1917, he was appointed field secretary of the Board of Home Missions. He was succeeded by Charles S. Freeman, who left First African in 1928. During Freeman's tenure, the membership of the church grew to over 500 people.

After the difficult years of the Depression, the congregation prospered again under the leadership of Sudor Q. Mitchell, who became the first African American to serve as a member of the Board of Foreign Missions. In 1943, the congregation moved again, this time to the old Tabor Presbyterian Church building at 18th and Christian Streets. After Mitchell's departure in 1947, the congregation called Shelton B. Waters to the pulpit. Waters presided over the congregation's move to 42nd Street and Girard Avenue in 1957; despite extensive renovations, the old Tabor Church building had been declared unsafe.

Waters left First African in 1969 to take an executive position at the synod level. Kermit E. Overton, who had served in Africa as a fraternal worker, succeeded him. He became the leader of Black Presbyterians United and was a founder of the journals Periscope and Periscope 2. During the 1970s and 1980s, he served as Philadelphia Presbytery moderator and held important posts within the synod and the General Assembly.