In 1866, the First Presbyterian Church was established. The first North Side services of this church were held in the North La Crosse school house, located at Caledonia and St. James Streets on June 10, 1866. During 1867, this school house was purchased and relocated to 911 Rose Street where it was remodeled to accommodate church needs. A dedication ceremony was held on August 9, 1868.

Several members of the First Presbyterian Church who lived in North La Crosse petitioned the Chippewa Presbytery on April 29, 1870, requesting a separate church from the South Side congregation. The request was granted and approval made May 1, 1870. The name was changed to the North La Crosse Presbyterian Church of La Crosse in 1877 and incorporated in 1878.

This church building was sold to St. James Catholic Church early in the 1890s. In approximately 1894, construction of a new church building, located at Avon and Logan Streets, was started. During this time, services were held in Wannebo Hall on the southeast corner of Clinton and Caledonia Streets. Additions of brick siding and stone trim were completed in 1906. The congregation purchased a manse at 1552 Avon Street in 1913. Until this time, the pastors had resided in rented homes. This manse was sold in 1948, and a new one constructed next to the church at 1347 Avon Street. Over the next several years, the interior and exterior of the church were improved and the steeple removed.

The facilities became too small to accommodate the church's needs. Land connecting George Street, North Salem Road, and Loomis Street was purchased from the La Crosse Catholic Diocese. Groundbreaking took place on April 26, 1964, and the first service was held on November 26, 1964. The dedication for the educational facilities, fellowship hall, and church located at 1327 North Salem Road was held on February 28, 1965. In November of 1965, a new manse was completed at 2627 Loomis Street. The old church manse on Avon Street was sold to the Church of the Nazarene in 1965. Additions were made to the sanctuary of the new church, pastor's study, secretary's office and work room in November 1977.