Greenwich House was incorporated in 1902 as the Cooperative Social Settlement Society of the City of New York by Mary Kingsbury Simkhovitch with Felix Adler, R. Fulton Cutting, Eugene A. Philbin, Henry C. Potter, Jacob Riis, and Carl Schurz. Working out of a renovated tenement house at 26 Jones Street, Greenwich House's first challenges were to work to reduce the debilitating infant mortality rate in Greenwich Village, then the highest in New York City, and to ameliorate the oppressive social conditions that attended the neighborhood's population congestion. Its first director, Mary Simkhovitch, agitated for better living conditions, playgrounds, child labor laws, and sanitary measures, and implemented the Settlement's programmatic scheme to address the pressing needs of the community. Two classic studies published in the pre?World War I years, Mary Ovington's Half a Man and Louise Boland More's Wage Earner's Budget: A Study of Standards and Costs of Living in New York City, were products of Greenwich House's Social Investigation Committee. The Tenant's Manual, published in 1903, was the first of its kind to document tenement laws and tenants' rights.

Beyond its pioneering work in housing reform, Greenwich House set programmatic innovations in other areas. The Nursery School, founded in 1921, was the first and prototypical program of its kind in New York City. Simkhovitch, an ardent advocate of cultural programs, believed the arts to be essential human services. By l917, when Greenwich House relocated to 27 Barrow Street, it offered music, theatre and fine arts programs onsite and also established art classes in many local public schools. The Greenwich House Arts Committee was initiated with the support of Mrs. Payne Whitney, who later founded the Whitney Museum.

By the end of the First World War, Greenwich House had clearly expanded its role beyond that of a small social service dispensary. Integral to its growth and success were its residents, the young social workers and middle-class reformers who lived in the settlement house and who frequently worked with promising leaders developed from the client population. In addition to its cultural agenda and housing reform activities, it provided vital institutional support for government programs, a function that further solidified in the l930's when many programs of the Works Projects Administration were housed at the Settlement.

Settlement houses, and their leaders, were also key advocates for reform. Mary Simkhovitch was no exception, her efforts were central to the passage of the U.S. Housing Act of 1937, which provided for federal aid to build low-income housing. Greenwich House has been a Village fixture for more than one-hundred years. Among its many thousand anonymous beneficiaries are a number of now familiar people including actors Kirk Douglas and Rip Torn, both of whom performed on the Greenwich House stage early in their careers, boxer Gene Tunney, who worked out in the gym, and former New York City mayor Ed Koch, who studied at the Music School (whose faculty included, over the years, such distinguished artists as Edgar Varese and John Cage.) In addition, Eleanor Roosevelt, Amelia Earhart and John Dewey, who served as head of the Greenwich House Education Committee, were frequent visitors in the Settlement's early years.