Oxford House was established by students from Keble and Balliol Colleges, Oxford University in 1884. They were influenced by Samuel Barnett's call for students to take time to work to better the lives of those affected by poverty in London's East End. While Barnett went on to open the neighbouring Toynbee Hall in 1885, the founders of Oxford House were concerned by the secular focus of Toynbee Hall and endeavored to set up their own operation which would serve the community with an Anglican emphasis. Oxford House was the first settlement house in the United Kingdom, hosting student residents who carried out work in the community.
Governed by a Council of Management (later a Board of Trustees), the original aim of the House was:
'A. To provide a centre for religious, social and educational work among the poor of East London; B. To undertake and carry on religious, social and educational work in London and elsewhere'.
In its early years, residents of Oxford House focused on providing clubs and activities for the local community, with regular services being held in the Chapel at the top of the House. During the Second World War, Oxford House served as a refuge and bomb shelter, and helped to organise shelter for local children in Wales, away from the bomb-scares of London. In the late 1940s, the House replaced its religious focus with a focus on social and community work, turning from settlement house to community centre. Residents were slowly replaced by organisations renting office space in previous accommodation rooms. The 1950s saw an Oxford House Community Association directing many community-based activities. In the late 1970s through to the 1980s, the House became more agile to the needs of the community, and several departments/ branches of work were initiated to help with local social issues of unemployment, homelessness, and racial segregation. In the 1980s and 1990s, the House sought to work with local Bengali and Somali communities, and was the site of the first Somali Week Festivals in London. The early 2000s saw the House branch into youth service provision for the London Borough of Tower Hamlets, however in the mid-2000s the House faced significant financial difficulties, and its social programmes were significantly reduced. From this point on, the House focused on its work as an arts space and venue for hire, as well as continuing to host many tenant organisations in its upper floors. In 2019 the House reopened after a large-scale renovation project. Oxford House hosts regular exhibitions and heritage events.