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Originally founded in 1956 as an “evening college” at Amundsen High School on Foster Avenue, the school was the result of community outcry for a two-year college for the then economically ailing community areas on Chicago’s northside.  The college quickly outgrew its location and, as Mayfair College, moved in 1961 to a former elementary school on Wilson Avenue with 4,000 day and evening students.

Continued growth resulted in the construction of a permanent campus at its present location, 1145 West Wilson Avenue, which was completed in 1976.  It was then Mayor Richard J. Daley’s press secretary who suggested naming the new campus Harry S Truman College after the 33rd President – a lifelong proponent of education, including community colleges.

The current campus consists of the original 1976 building; a complex that houses the school’s technical education center, a theater, and a sports complex with a gymnasium and fitness center; and the Larry McKeon Student Services Building, completed in 2010.  Certified Silver through the Leadership in Energy Environmental Design Program of the US Green Building Council, the building is named for longtime friend of the college, State Representative Larry McKeon. The building consolidates the campus’ student service departments under one roof and includes a 1,100 parking space structure for students, faculty and staff.

As part of the City Colleges of Chicago’s College to Careers initiative, Truman College's emphasis was designated as education, human and natural sciences in 2014, offering a combination of certificates and associate degrees in fields tailored for those first entering the education profession as well as for professionals in need of continuing education.