The university was founded on 1 October 1888—ten years after the liberation of Bulgaria—to serve as Bulgaria's primary institution of higher education.

History, geography, Slavic philology, philosophy and pedagogics, mathematics and physics, chemistry, natural sciences and law were also taught.

The plans were developed by Nikola Lazarov and revised by Yordan Milanov, who also directed the construction, but died before the official opening on 16 December 1934.

After the political changes of 9 September 1944 and the emergence of the People's Republic of Bulgaria, radical alterations were made in the university system of the country.

Three new faculties were founded in 1947, one of forestry, one of zootechnics and one of economics and major changes occurred, with many departments seceding in later years to form separate institutions.

In 2001, the Sofia University was the first Bulgarian Athenaeum to open a Theological Faculty ruled by the national Orthodox Church after the fall of communism.