Organized on January 22, 1852, the First Congregational Church is the second oldest church in La Crosse. On this day, twelve Congregationalists and Presbyterians formed a union church, and at the same time and place the First Baptist Church was being established at the home of S. T. Smith. The First Congregational Church became a member of the Presbyterian and Congregational Convention of Wisconsin in October of 1855. A separate Presbyterian Church was organized in 1866.

Until a lot at the southeast corner of Fourth and Jay Streets was donated by the Peter Cameron estate for the completion of a church in December 1855, the members met at various locations such as the old wooden courthouse and the Old Third Ward brick school house. In 1870 the church at Fourth and Jay Streets was sold to the Norwegian Lutheran Church. A new church was built on the corner of Seventh and Main Streets in an American Gothic style. This building was partially razed after it was found to be structurally unsound, leaving only the 1931 addition across the back. The third church building was constructed at Losey Boulevard and Main Street with a dedication of the new church being held on September 13, 1953 (Haas, Charles E. Bless the Work of Our Hands. La Crosse, WI: First Congregational Church, 1984). The church at 2503 Main Street is a multi-level, flat-roofed structure with a Winona stone exterior. It is also complete with a large educational wing. Remodeling efforts of the fellowship hall and sanctuary have been accomplished in the 1990s.