The college was established by an English industrialist and philanthropist Sir Josiah Mason in 1875. The building of the college in Edmund Street, Birmingham was designed by Jethro Cossins and opened on 1 October 1880 and was marked by a speech by Thomas Henry Huxley. In the speech, Huxley considered the opening of the college as a victory for scientific cause and supported Mason's antagonistic views on the classics and theology. The college developed various liberal and vocational subjects, but forced out the artisans. The medical and scientific departments of Queen's College, Birmingham moved to the nearby Mason Science College.
In 1898 it became Mason University College, with Joseph Chamberlain becoming the President of Court of Governors of the college. In 1900 it was incorporated into the University of Birmingham. Students at the College were awarded their degrees by the University of London until the University of Birmingham was established and received degree awarding powers in its own right.
In 1881 Charles Lapworth became the first professor of geology at the college. In 1891 physics professor John Henry Poynting successfully calculated the mean density of the Earth.
The Mason College building housed Birmingham University's Faculties of Arts and Law for over half a century after the founding of the University in 1900. The Faculty of Arts building on the Edgbaston campus was not constructed until 1959-61. The Faculties of Arts and Law then moved to the Edgbaston Campus.
After the Second World War the style of architecture was not as appreciated as it is now. Paul Cadbury referred to it in 1952 as a neo-gothic monstrosity and expected it to be demolished within 50 years. In the event it was demolished in 1964, along with the original Central Public Library and the Birmingham and Midland Institute, as part of the redevelopment within the inner ring road. The former Central Library stood on the site of the old college, the library having moved to a new site in 2013; the building was demolished in 2016.
During the first academic session of the college in 1880 courses in physics, chemistry, biology and mathematics were offered to students. By 1881 courses in geology and mineralogy, botany and vegetable physiology, engineering, English language and literature, Greek and Latin, and French and German language and literature were also available. From 1882 Medical students at Queen's College, Birmingham were able to attend classes in botany, physiology and chemistry, and in 1892 the medical faculty of Queen's College was transferred to Mason College. There was also a short-lived department of 'Mental and Moral Science', which was not successful despite funds being gifted specifically to support the endeavor in 1882.
^Eric Ives et al, The First Civic University: Birmingham 1880-1980 An Introductory History (Birmingham, 2000), p. 12
^Warner, D.; Palfreyman, D., eds. (2001). The State of UK Higher Education: Managing Change and Diversity. Buckingham: Society for Research into Higher Education & Open University Press. p. 30. ISBN978-0335206599.
^Ballard, Phillada (2009). Birmingham's Victorian and Edwardian Architects. Oblong Creative Limited. p. 231. ISBN0-9556576-2-8.