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Denison House was a woman-run settlement house in Boston's old South Cove neighborhood. Founded in 1892 by the College Settlements Association, it provided a variety of social and educational services to neighborhood residents, most of whom were immigrants. Several notable women worked there, including Nobel Prize winner Emily Greene Balch, labor organizer Mary Kenney O'Sullivan, and pioneering aviator Amelia Earhart. The original site at 93 Tyler Street is a stop on the Boston Women's Heritage Trail.

Denison House was established in 1892, donated by Cornelia Warren, as one of the earliest branches of the College Settlements Association. The CSA had been founded in 1887 by a small group of Wellesley College faculty and alumnae including noted pacifist Emily Greene Balch, labor organizer Vida Scudder, and the writer and college professor Katharine Lee Bates. It was named for Edward Denison, an English social reformer who advocated living among the poor. Balch was an admirer of Jane Addams, whom she had met at an Ethical Culture Society gathering; Denison House was modeled after Addams's Hull House in Chicago. Its mission was to provide Boston's poor with social services and education, not only for philanthropic purposes but to break down class barriers. The women hoped that bringing people of different backgrounds together under one roof would further the purpose of democracy, which they defined as "a free flowing life between group and group".

The original Denison House was located at 93 Tyler Street, a red brick row house across from the old Josiah Quincy School. It quickly outgrew that space, and the adjoining house was added on. By the 1920s it occupied five row houses with a shared entrance at number 93. Its first head resident was Balch herself, who served there briefly before returning to academia.

Balch was replaced as head resident by Helena Dudley, who served from 1893 to 1912. Arriving during the Panic of 1893, Dudley immediately set to work organizing the house as a relief agency that could distribute such basic necessities as milk and coal. Under her direction, Denison House became an important neighborhood center, offering classes in nursing, English literature, crafts, cooking, and carpentry, as well as sports and a summer camp for children, and clubs for adults. It had a library, a gymnasium, and a clinic. Later, Dudley cooperated with Robert Archey Woods and other residents of South End House—Boston's first settlement house, located just a few blocks away—to hold art exhibitions, conduct housing investigations, and campaign for public bathhouses and gymnasiums.

Local men and women who frequented Denison House, most of whom were immigrants, were encouraged to celebrate their heritage through cultural festivals and craft exhibitions. One such exhibition took place at the Pennsylvania Museum and School of Industrial Art in 1917. On display was "the work of Italian, Syrian, Greek and Armenian craftsmen and craftswomen, in silver, leather, linen, silk embroideries, etc., from old designs copied in part from treasure pieces in palaces, museums and private collections in Europe and America." The exhibition was reportedly a great success, with many of the items being sold. The teenaged boys of the Denison House dramatic club performed Shakespearean plays to raise funds for renovations, and received encouraging reviews in the Boston Globe.

Among the early residents of Denison House was the labor organizer Mary Kenney O'Sullivan, who lived there for several years in the 1890s with her husband and three children. O'Sullivan, Dudley, and Scudder were among the founding members of the Women's Trade Union League in 1903. Mary Morton Kehew, president of the Women's Educational and Industrial Union, was treasurer of Denison House in the late 1890s, and the Christian Socialist writer W. D. P. Bliss gave a speech there in 1898. In an address at Wesleyan Hall, Dudley said that the college women had learned, through their work at the settlement house, "of the conditions which press upon the wage earners. We have found women making shirts for 37 and a half cents a dozen...and it is because of this knowledge that we have become interested in trade unions."

During Dudley's tenure several trade unions met regularly at Denison House, and in 1904 she hosted Catherine Breshkovsky, "grandmother of the Russian Revolution", at Denison House for several weeks. In 1912 Dudley and O'Sullivan paid the bail of $500 each for Joseph Ettor and Arturo Giovannitti, leaders of the 1912 Lawrence textile strike who had been arrested on trumped-up charges. Another Denison House worker, Vida Scudder, also supported the Lawrence strikers, and gave a widely publicized speech at a strike meeting. Wealthy donors were troubled by the house's connections to organized labor, and as fundraising became increasingly difficult, both Dudley and Scudder were forced to resign their positions.