First Presbyterian Church was organized April 13, 1824, by Scots-Irish settlers. The sanctuary, erected in 1827, is the oldest in continuous use in Alabama. Its Georgian Gothic style remains essentially unchanged. The brick walls are laid in Flemish Bond and massive hand-hewn beams are joined with wooden pegs. A rare feature is the original wrap-around slave gallery, supported by two levels of columns. The walls were reinforced with iron bars after the 1874 tornado and stained glass windows were added in 1904. The church is listed in the Historic American Buildings Survey and the National Register of Historic Places.
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Notable Tuscumbians who were members include: the Arthur Keller family, whose infant daughter Helen Keller was baptized here in 1880; Brig. Gen. James Deshler, CSA; Alabama Governor Robert Burns Lindsay; Judge John Anthony Steele, delegate to the State Secession Convention and Thomas Limerick, first mayor of Tuscumbia and original trustee of the church. Revivals led by Presbyterian evangelist Daniel Baker in 1839 and 1843 added over 100 members. Committed to Biblical and confessional belief and a deep desire to share grace and truth to all, the church has been a recipient of God's grace working in godly leaders.