Formally organized on January 6, 1817 in the home of Mrs. Elizabeth Minor, First Presbyterian Church was formed under the leadership of the Rev. John Knox Witherspoon. Included among the charter members were the daughter and granddaughter of the Rev. Jonathan Edwards, D.D.
In 1819 log number 309 on New Street was purchased. Construction of the sanctuary began June 9, 1819 with the laying of the cornerstone by Master Masons. Uriah Sandy was contractor, assisted by Martin Stevenson and John Dewey who were members of the church. The building was completed in late 1821 and dedicated on January 6, 1822. Numbered pews were offered for sale or rent with "visitor pews" provided on both sides of the pulpit.
To the right of the sanctuary is the Session House, built in 1858 for the sum of $1500. During the Civil War the sanctuary was used as a hospital for sick and wounded Union soldiers with planks being placed over the pews or beds. Restoration work was required in 1866 and was marked by the installation of Victorian-style gaslights and stained woodwork. In 1936 the restoration and reinstallation of the original pulpit was completed.
In addition to its own growth and outreach, First Presbyterian Church aided in the establishment of Ebenezer Church in 1878 and following World War II in the establishment of Neuse Forest (1946) and West New Bern (1948) churches.