This congregation was organized on April 28, 1857, with the first meeting held in the Old Court House and subsequent meetings in the Woodman's Hall at Washington and 2nd Avenue (which later became the St. James Hotel) and another nearby building. They erected a church on Nicollet at 4th Street, dedicating it on December 22, 1858. This building burned on the night of April 3, 1860, in retaliation, some felt, for pastor H. M. Nichol's temperance work. The congregation continued to meet in the Free-Will Baptist Church, in Fletcher's Hall (2nd Avenue and 1st Street), and in Harrison Hall (Washington and Nicollet), eventually erecting a new church on the original site in 1863. This church was subsequently enlarged in 1866. The growing congregation erected a new church seating 1200 at Nicollet and 8th St., dedicating it on October 10, 1875. The congregation moved into the Y.M.C.A. Building on 10th Street in 1885, and on March 14, 1909, moved into a new church at Nicollet and Groveland Avenue. The congregation, still housed in this building, remains extant at the time of this writing (2015). Two monumental events in the church's history include 1905 when the church hosted W.E.B. DuBois as well as in November 1913 a branch of the NAACP was organized at Plymouth.
The congregation was actively involved in home missionary and Sunday school work, founding several organizations, including Bethel Mission (later renamed Pillsbury Settlement House), Immanuel Sunday School (later Drummond Hall), North Mission, and a Newsboy's Sunday school. It also contributed to the founding of several other congregations, including the Park Avenue Congregational Church (earlier names for this congregation were the Plymouth Chapel, the Vine Street Church, Second Congregational, and finally Park Avenue Congregational). Pilgrim Church, was founded in 1863 as a Sunday school in a rented hall in North Minneapolis on 20th Avenue North and 2nd Street. The church was organized on September 24, 1873, as Pilgrim. In October 1890, 43 Plymouth members founded the Lowry Hill Church. Plymouth also founded a Sunday school in Alexandria, Minnesota, in 1867.