The First Baptist Church in Salem, Massachusetts, was formed when early in 1804, a small group of Baptists, mostly members of the Danvers church, began to meet together occasionally for prayer and conference. There were only ten or twelve, mostly women; they had no public room to gather. The husbands of two of the women, Michael Webb, and Edward Russell, offered to create a place for them to worship. A lot of land was purchased and a moderate sized framed building erected for their use. In April 1804, Lucius Bolles began preaching in the small unfinished wood building. By December of that year, the number of baptized members had increased to twenty-four, including himself, and early the following month they were publicly recognized as a church and he was ordained their pastor.

In August, 1826, an associate pastor, the Rev. Rufus Babcock, Jr., of Poughkeepsie, New York, was publicly recognized. In August, 1834, the Rev. John Wayland was settled as the sole pastor of the church, Dr. Bolles having moved his family to Boston, and resigned the office of senior pastor. Mr. Wayland retained his place for seven years and was succeeded in 1842, by the Rev. Thomas D. Anderson.

The First Baptist Church stood at 56 Federal Street for years. The oldest portion was built in 1805, after a small building on the same site proved too small for the growing congregation. In 1827, the building was enlarged and fitted out with a three-stage Federal tower topped by an octagonal dome. Around 1850, a chapel was added. The tower was removed in 1926, due to cost of repairs.

The Commonwealth of Massachusetts paid the church two million dollars in 2008 for the church building after prolonged negotiations. The original part of the church was moved a short distance to the corner of North and Federal Streets and converted to a law library, part of the J. Michael Ruane Judicial Center. With this money, the church members were able to secure a new church location at 292-296 Lafayette Street. They took the pews, a few pianos, an organ, and a stained-glass window in memory of an early Baptist missionary, Adoniram Judson, from the old church.