The Meridian Union of the Women's Christian Temperance Union (WCTU) was composed of women of the Central Avenue Methodist Episcopal Church, whose members included William Vincent and Mary Wheeler. When the Meridian Union decided to pursue mission work among "homeless or fallen" girls, Mrs. Wheeler, who was the treasurer, was appointed to serve on the committee responsible for accomplishing this task. Aware that the work they were beginning was a first in the city, yet undaunted by the unpopularity and difficulty of accomplishing the task, the women decided that religious services should also be offered to men, women and children so that "the poor, the down trodden, the discouraged and those who on account of poverty could not attend a church and feel welcome" would have a place of worship. A building which would accommodate these goals was found at 57 East South Street, located in the manufacturing district of Indianapolis. The building formerly housed the Elm Saloon and, in fact, the back door to the old saloon was "displayed for many years near the entrance to the mission as an attraction to transient men." The upper floor of the building was used as the home for "friendless women" or unwed mothers and Celia Smock was employed as the matron. The large storeroom on the first floor was used for nightly religious services. When The Door of Hope opened its doors and held its first service on October 13, 1893, William Vincent Wheeler was one of the attendees. Because of his wife's involvement, Wheeler was familiar with the work and volunteered to help with the church services.

Mr. Wheeler, a salesman for the Layman-Carey Hardware Company, was also a well-known evangelical lay-preacher who gave sermons under the big beech tree inside the entrance to Greenlawn Cemetery." Under Wheeler's direction and with the approval of the women of the Meridian WCTU, services were extended to include a Sunday school, as well as a sewing school which taught young girls to sew and helped older girls improve their sewing skills. The fabrics were donated and the girls were allowed to keep the clothes that they made for themselves. The women who volunteered as teachers in the sewing school also mended the clothing which had been collected for distribution to the poor. Wheeler sought to serve the poor by serving the entire family and went each day to court proceedings to seek out those men who, although in current difficult circumstances, were seeking a way to improve their lot, reasoning that if he could help the men straighten out their lives, their families were sure to receive the benefits. The Rescue Mission's purpose was to be a charitable organization serving the material and spiritual needs of poor individuals and families in Indianapolis through Christian evangelism and conversion.

The mission, now known as The Rescue Mission and Home, continued to grow and Wheeler continued as the part-time superintendent. In the year and a half The Door of Hope home for friendless women had been in operation, more than 165 girls had been helped. In 1895, the home was moved to 132 N. Alabama Street. It continued for several more years under the direction of Mrs. Frances A. Potter and was then turned over to the Florence Crittenton Home. Also in 1895, with the unanimous vote of the women of the WCTU, Wheeler assumed the full-time superintendency of the mission as a paid position, resigning from Layman-Carey Hardware Company. At this time, a Board of Directors was formed consisting of men who were leaders in the Indianapolis community, giving the mission new respect and status. The mission was moved to 49 East South Street and while expanding services to families, still did not offer housing for the homeless that Wheeler strongly felt was necessary.

In 1901, Wheeler began a building campaign to finance the construction of a new home for the mission, stating "Our city is growing and our field is enlarging, and we would like very much to be able to push our work and meet the demands upon us." By 1905, most of the necessary $17,000 had been raised and the building was begun at 443 East South Street, which, when completed later that year, would provide a 400-seat chapel, a 150-seat auditorium for the children's Sunday school, rooms for temporary housing, the girls' sewing school and the mother's meetings.

From its beginnings the mission coupled its charitable work with Christian evangelism and programs to develop a sense of self-sufficiency among the poor, following Wheeler's belief that religion and a strong work ethic were essential for the poor to end their dependence on charity. Women were taught housekeeping skills and indigent men were employed in the mission's wood yard. The mission also provided food, clothing, furniture, assistance in locating inexpensive housing and other forms of charitable assistance. Mission support was derived from the local protestant churches with later involvement by the Indianapolis Community Chest.

Wheeler continued as superintendent until his death on Christmas Day 1908. The following week, the Board of Directors changed the mission's name to Wheeler Rescue Mission in deference to its founder. Wheeler's death marked the beginning of a fifteen-year period of instability in the organization during which it underwent several changes of name, location, leadership and philosophy. In 1918 it merged with the City Mission to become the Wheeler City Rescue Mission. As a result of this merger, the mission placed greater emphasis on evangelistic revival meetings. In 1920 it moved to the Empire Theater on East Wabash Street in order to have a more suitable facility for the performances of traveling evangelist shows. By 1921, though, the enthusiasm for revival meetings had waned and the mission's survival was in doubt.

The Board of Directors moved the mission to 134 North Delaware Street and in 1923 appointed Herbert E. Eberhardt as superintendent. Eberhardt's appointment marked a return of the mission to its original focus on indigent men and families. During Eberhardt's tenure the mission began a radio program on WFBM, successfully raised funds to build a permanent residence at 245 North Delaware Street and expanded its services to include a men's Sunday School. Under Eberhardt's leadership the mission became a member of the International Union of Gospel Missions, an organization which promoted Wheeler's principles of service. Membership requirements included recommendation letters from the community's Protestant churches which helped to give the mission legitimacy and a base for funding.

Under Eberhardt the mission focused its energies on assistance to prisoners and transient men. The prison program included weekly jail/prison visitations and the sponsoring of prisoners upon their release. Sponsorship responsibilities included providing food, clothing, shelter and referrals to private and government employment and assistance agencies. Similar support was given to transient men. Community programs that evolved from the mission's work with the families of prisoners and indigent men were the children's Sunday School, children's Saturday Morning Bible School and Saturday Lunch, Youth Fellowship, and the women's division. These programs attracted area residents and the mission gradually became a neighborhood community center.

The mission never refused aid to anyone; however, prior to about 1960, only emergency assistance was provided to African-Americans. Herbert Eberhardt was instrumental in gathering support for the establishment of Good Samaritan Mission, a facility to aid African-Americans in need. Eberhardt solicited religious materials and food vendors for donations and requested monetary donations from area churches. He offered advice on managing the new mission to its superintendent, Rev. Grover C. Mills, and on March 29, 1944, was the guest speaker at Good Samaritan's dedication ceremonies.

Upon Eberhardt's resignation in 1944, Leonard C. Hunt became superintendent. Under Hunt's administration the mission's activities were expanded. Frances Hunt organized a women's auxiliary, comprised of women from more than 80 local churches, to serve women's needs. A children's summer camp was built in 1950 and, after Hunt's death in 1978, was renamed Camp Hunt in his honor.

Succeeding Hunt were Bill Brown in 1978 and Richard Alvis in 1988. Brown began a gradual shift in mission services as the mission's clientele became younger, less trusting and less willing to work. Seeking to meet the new challenges presented by the problems of drug abuse, mental and emotional illness, AIDS and long-term homelessness, the mission reorganized and refocused its programs to serve the changing needs of the men, women and children who came seeking help. Among these programs were youth clubs, a shelter for battered women and abused children and a mother's club.

Societal changes and the new programs required a reorganization of management and staff. The mission began employing more paid professional staff with less reliance on volunteers. A decentralized approach to management placed greater responsibility with each program director and freed the administrator's time for fundraising and mission expansion. Completing the mission's transformation in 1990 was a name change to Wheeler Mission Ministries, reflecting the mission's contemporary outreach organization.

In 1991, the Dearborn Hotel, a ten-story hotel with a full-sized gymnasium located at 3208 East Michigan Street, was purchased for use as a youth and family center. Immediate renovation was commenced and in January 1992, the first mission program moved into the hotel and marked the use of the hotel as a full-service facility for needy families and young people.

By 1993, the centennial of the founding of the mission, the programs and services of Wheeler Mission Ministries were reaching, teaching and serving many thousands of people in the Indianapolis area. The Board of Directors had grown to nineteen active members and six emeritus members. Staff had expanded to include youth field workers who were in charge of individual youth clubs and their activities. The downtown mission maintained its goal of serving each transient man with a personalized approach to resolution of his problems. The mothers' club which met each week for Bible study, fellowship and prayer had grown to a weekly average of 102 women. Family camp sessions included more than 40 families and hundreds of children benefited from Camp Hunt's programs. The mission served an average of 500 persons a day and provided 20,000 nights of lodging, 25,000 articles of clothing, and 80,000 meals with the area churches and businesses providing 15% of the million dollar budget and private donations supplying the rest.