Early in the 17th Century, the Rev. John Lothrop and his followers left England for these shores seeking religious independence. They settled first in Scituate and a few years later come to Barnstable, arriving in 1639. They constructed their first meetinghouse in 1646 on Coggins' Pond, about a mile west of the present church.

By the early 1700's the town had grown sufficiently large to support two parishes. Members in the East Precinct erected a building on this present site on Cobb's Hill, and another building was constructed in the west end of Barnstable. In 1717, the original church became two churches.

In the early 19th Century there was considerable theological debate in the "churches of the standing order" in New England. Many churches actually split over this debate, the traditionalists becoming Congregationalists and the liberals becoming Unitarians. Already recently divided along geographic lines, the church in Barnstable did not undergo this split. The church in the West Parish followed the line of tradition and is today a Congregational church. This church, then known as the East Parish, leaned toward the liberal side of the debate and later became identified as a Unitarian church.

In 1836 the original Cobb's Hill meeting house was removed and a new, larger one was constructed. It was destroyed by fire in 1905. The present edifice was dedicated in 1907. It was designed by Guy Lowell, the architect of the Boston Museum of Fine Arts. The Parish Hall was constructed in 1960. It is now named Warren Hall in honor of the Rev, Kenneth R. Warren, who served the church from 1953 to 1991. A further addition to the west end of the building was built in 1979.

The church is affiliated with the Unitarian Universalist Association, formed in 1961 by the merger of the American Unitarian Association and the Universalist Church of America.