It was founded on 28 March 1919 by combining the previous General Lecture System (Allgemeines Vorlesungswesen), the Hamburg Colonial Institute (Hamburgisches Kolonialinstitut), and the Academic College (Akademisches Gymnasium).

The main campus is located in the central district of Rotherbaum, with affiliated institutes and research centres distributed around the city-state.

At the beginning of the 20th century, wealthy individuals made several unsuccessful petitions to the Hamburg Senate and Parliament requesting the establishment of a university.

Senator Werner von Melle worked towards the merging of existing institutions into one university, but this plan failed.

He and Rudolf Ross advocated for education reform in Hamburg, and were able to pass a law establishing both the university and an adult high school.

The student population reached several thousand, and the growing popularity of the university drew scholars such as Albrecht Mendelssohn Bartholdy, Aby Warburg and Ernst Cassirer to Hamburg.

Massive political influence by the Nazis followed, including the removal of books from the libraries and harassment against alleged enemies of the regime.

[3] At least 10 Hamburg students were suspected of working with the White Rose and arrested; four died in custody or were executed.

A commemorative plate depicting the foyer of the lecture hall, designed by Fritz Fleer, was produced in 1971 in their memory.

[citation needed] A wave of protests during the student movements of 1968 resulted in a reform of the university's structure.

The involvement of students and staff in the administration was also increased, and the office of Rektor was abolished in favor of a university president.

[3] The main campus in the Rotherbaum quarter was completed with additional construction in the 1970s, including the Geomatikum building and the Wiwi-Bunker (named for its bunker-like architecture).

The implementation of the Bologna process, an effort to ensure comparability of standards across European institutions, was another major point of contention during that decade.

Several departments are located in other quarters: Physics is spread over branches at Jungiusstraße, Bergedorf (along with the Hamburg Observatory) and Bahrenfeld (with the world-renowned DESY and other facilities).

It owns a large number of special collections and items of historic value, including medieval manuscripts.