St. Luke's United Methodist Church can trace its beginnings to a small group of Methodists living in North La Crosse in the year 1856. The group did not have a formal meeting place, but was under the guidance of the Onalaska Methodist "Circuit." Meetings were held in individuals' homes. The first formal meeting place was a schoolhouse at 927 Rose Street in La Crosse. A membership list from 1858 lists twelve members of the group: Albion Clark, Mrs. Clark, Cyrus Lambert, Catherine Lambert, Leander Soules, Mrs. Soules, Elizabeth Ghetts, Mrs. M. A. Knox, Susan Carr, Mrs. Whitbeck, Mrs. Mary Collins, and Mrs. Clarissa Boardman.

In 1866, land was purchased on present day Caledonia Street from William R. Sill for $75. The first section of the church was built in 1867 and was known as the La Crosse Second Church. A small parsonage was built in 1886 close to the church. A second parsonage, at 2420 Wood St., was used from about 1952 to 1965.

In 1887, the original church building was remodeled, pews were added, and an addition to the building was made. The church was renamed the Caledonia Street Methodist Church in 1889. The church continued to be served by the Onalaska Circuit until 1874 when it became independent.

In 1894, this congregation sponsored a mission church on French Island. Services were held there for fifteen years before the mission church was sold.

By 1917, membership in the church had grown to a point that the facilities were inadequate for church programs. Sunday School classes met all over the sanctuary, in the kitchen, and in the parsonage. The church was remodeled that year at the cost of $7000 by adding a basement under the church which included a social room, a kitchen, two bathrooms, and a coal burning furnace. The upstairs sanctuary was also redecorated.

While many pastors served the Caledonia Street Methodist Church over the years, the pastor who served the longest was Rev. Hugh R. Kinley. Kinley began his work in 1923, and became a popular minister among his congregation. Members of the congregation requested that he be allowed to continue his work there when opportunities for transfer to another congregation arose. Kinley passed away on July 26, 1943.

St. Luke's faced numerous financial difficulties over the years. During Rev. Kinley's tenure, there were times the congregation was unable to pay him his full salary. After Kinley's death, the congregation continued to have difficulty generating contributions so bills could be paid. In addition, the church building was deteriorating. Birds and hornets entered the church through broken windows in the church.

In 1950, members Raymond and Myrtle Bice, who were late for Palm Sunday services, decided to enter the church through the basement in order to quietly make their way upstairs to the rear of the sanctuary. The Bices heard a cracking sound in the basement ceiling and discovered that beams supporting the floor of the sanctuary were near collapse. Word was sent to Rev. George Bell that the congregation must quietly exit the building. It was discovered that termites had significantly weakened the structure. Repairs were made so the building could continue to be used, but the congregation's board of directors, under the guidance of Rev. Lee Holmes, instituted a building fund on March 1, 1953.

A ground-breaking service for a new church building was held on March 23, 1958. The new church, designed by Hackner, Schroeder and Associates, was built in two phases and the educational unit was built first. This section included a social hall, classrooms, kitchen, youth room, chapel, and offices. Once the educational unit was completed at the end of 1958, church services were held in the social hall, and the old church building was razed in 1959.

A consecration service for the new building was held on Feb. 8, 1959. On that same date, the congregation voted to change the name of the church from the Caledonia Street Methodist Church to St. Luke's United Methodist Church.

The second phase of construction, during which the sanctuary was built, began in April 1962. Work was completed that year, and the first service was held in the new church on Dec. 23, 1962. The complete cost of this construction project was $300,000 with the sanctuary making up $110,000 of that cost. A consecration service for the sanctuary was held on Feb. 10, 1963.

St. Luke's was host to the 110th session of the West Wisconsin Annual Conference from June 9-12, 1964. 125 pastors and 150 laypeople representing 256 Methodist churches in Wisconsin met to discuss important issues, such as civil rights, which were confronting the Methodist Church at the time.

Between 1965 and 1966, a new parsonage was built at 1220 Sill Street with volunteer labor donated almost entirely by the members of the congregation. The new parsonage was dedicated on Sunday, May 22, 1966.

In 1980, Raymond C. Bice, Sr., wrote a detailed history of the congregation entitled The Story and History of St. Luke's United Methodist Church 1856-1980.

St. Luke's extended an invitation to Rev. Dorothy Kuechmann, of the First Congregational Church in La Crosse, to help with their social programs, and as of January 1980, Kuechmann began a shared ministry between the two churches. She assisted St. Luke's pastor, Rev. Billy Bross, with services and developed a senior activity program for senior citizens in the community. Kuechmann served St. Luke's until Sept. 1986 and resigned to work on other projects.

In 1994, Rev. William R. McBride expressed concern about the loss of membership at St. Luke's and instituted a contemporary worship service lead by the Great Awakenings Band. The goal was to reach out to people between 29 to 47 years old who were not currently attending church. These services were eventually discontinued, but contemporary worship services resumed once a month during the fall of 2003.

Another outreach program designed to draw younger people into the congregation, began in 1996, involved serving a Wednesday night supper with a worship service following the meal. This program was discontinued after a year or two.

The Monday's Meal program was started in Sept. 2002 as an ecumenical effort involving several congregations. As of Oct. 2004, this program continues. Free meals are served on Monday evenings at St. Luke's Church to any one who wants them. Sometimes additional food distribution takes place after the meal.

In January 2004, Rev. Dominik Israel arrived from India to become pastor of St. Luke's. Israel met with leaders of the church to develop a vision and mission statement for the congregation.