The town of Lancaster and the First Congregational Church in Lancaster were established on November 28, 1653, with the signing of a civil covenant by the town’s first settlers. In 1654, the town called Joseph Rowlandson, a recent graduate of Harvard, to be the first minister. He married Mary White, the daughter of a wealthy settler, in 1656 and was officially ordained in 1660. The first meeting house and parsonage were also quickly constructed following the installation of Rowlandson. In 1676, as part of King Phillip’s War, Native Americans attacked the Lancaster garrison. During the attack 12 were killed and 12 more captured, including Mary Rowlandson, and a number of buildings were burned including the meeting house. After 11 weeks, Mary Rowlandson was ransomed back to her family and an account of her captivity was published in 1682.

The second meeting house was constructed in 1684 on the same location as the first. It did not survive long as it too was razed during an attack carried out by Native Americans in 1704 as part of ongoing hostilities between France and England. A third meeting house was constructed in 1706 and the first minister to preach in the new building was Rev. John Prentice who was installed in 1708. During the First Great Awakening, Rev. Prentice kept the Lancaster Church aligned more closely with the traditionalist "Old Lights" than with the revivalist "New Lights." The third meeting house was torn down in 1743 and swiftly replaced by the fourth meeting house that same year. Rev. Timothy Harrington was the minister of the Lancaster church during the American Revolution. In 1777 he was accused of being a Loyalist in part because "he was in charity with a professed Roman Catholick." The chargers were dropped after Harrington gave an impassioned defense in which he pointed to the principals of religious freedom.

Due to the advanced age and failing health of Rev. Harrington, the town voted to settle a junior minister in 1792. In 1793 the town voted to accept Timothy Thayer as the new minister and he was ordained in the summer of that year. Rev. Thayer was a member of the Unitarian movement and almost immediately began to liberalize the church and make membership into the church significantly easier. Due to the move towards Unitarianism, some members of the church withdrew and formed the Evangelical Congregational Church of Lancaster in 1839. The fifth, and final, meeting house was built in 1816 on the Lancaster green and on January 1, 1817 a dedication ceremony was held. The meeting house was designed by Charles Bulfinch, one of the earliest American-born professional architects, and was entered into the National Register of Historic Places and designated a National Historic Landmark in 1970.

The First Congregational Church and Society were legally incorporated into a single legal entity, the First Church of Christ, around 1908. Beginning in 1918, the First Church of Christ and Evangelical Church held three union services annually, though the practice was discontinued in 1976 at the behest of the Evangelical Church. In 1952, the Rev. Dr. Alexander St. Ivanyi was ordained as the minister of the First Church of Christ. Before joining the church, Ivanyi had been part of the Hungarian anti-Nazi resistance during World War II, was a member of the Hungarian Parliament after the war, as well as the bishop-vicar of the Hungarian Unitarian Church. He was forced to leave flee Hungary after the communist takeover of the state. In 1970, during Rev. Ivanyi’s tenure, the First Church of Christ voted to join the Unitarian Universalist Christian Fellowship. Rev. Tom Wintle, who served as minister from 1975-1995, also helped create the Lancaster Historical Society. The First Church of Christ, Unitarian, in Lancaster continues to serve the local community today.