Mary Van Kleeck was born on June 26, 1883 in Glenham, New York. Upon graduation from Smith College in 1904, she began working with the College Settlement Association. Following her work as industrial secretary of the Alliance Employment Bureau, she was hired by the Russell Sage Foundation as head of the Committee on Women's Work. In addition to being one of the earliest foundations in the United States, the Russell Sage Foundation was also notable for the number of women on its staff.

In 1916, Van Kleeck became director of the newly established Department of Industrial Studies at the Russell Sage Foundation, a position she would hold for over 40 years. Throughout her life, she dedicated time and effort to various organizations aiding workers, both secular and religious, such as the American Civil Liberties Union and the Episcopal League for Social Action.

Mary Van Kleeck died on June 8, 1972 in Kingston, New York.