Father Idzi Radziszewski founded the university in 1918. Vladimir Lenin allowed the priest to take the library and equipment of the Saint Petersburg Roman Catholic Theological Academy to Poland to launch the university just as Poland regained its independence.

The aim of the university was to be a modern place of higher education that would conduct research in the spirit of harmony between science and faith. The university sought to produce a new Catholic intelligentsia that would play a leading role in Poland.

The number of students increased from 399 in 1918–1919 to 1440 in 1937–1938.This growth was interrupted by the outbreak of the Second World War and Nazi Germany's occupation of Poland. Of all the universities located in the German-occupied territory, the University of Lublin was the only one to resume work in October 1939. On 23 November 1939, the Nazis executed a number of academic workers, among others, professors Michał Niechaj and Czesław Martyniak.