The University was founded on October 1, 1946. Initially, it had 320 students enrolled in 5 faculties: Physics and Mathematics, Geology and Pedology, History and Philology, Biology, Chemistry. There were 35 teachers working in the 12 departments. Among the founders of the university were Macarie Radu and Mihail Pavlov.

In 1969, the State University of the Republic of Moldova joined the International Association of Universities as a plenipotentiary member. USM’s prestige on the international stage was further enhanced by the recognition of 14 distinguished individuals in science and culture from 9 countries around the world, who were awarded the title of Doctor Honoris Causa of USM. The State University of the Republic of Moldova has entered into more than 60 cooperation agreements in the field of education and science with university centers in 25 countries. Young people from around 80 countries have studied at USM.

Over the years, additional faculties and structures have been established beyond the original ones:

• Faculty of Economics (1953, 2002);
• Faculty of Law and Faculty of Engineering and Technology (1959);
• Faculty of Foreign Languages and Literatures (1964);
• Faculty for the instruction of foreign students (1967);
• Computing Centre (1973);
• Faculty of Journalism (1980);
• Central University Library and Faculty of Philosophy and Psychology (1994);
• Faculty of Political Science (1995).