The Great Schism of 1378 made it possible for Heidelberg, a relatively small city and capital of the Electorate of the Palatinate, to gain its own university. The Great Schism was initiated by the election of two popes after the death of Pope Gregory XI in the same year. One successor resided in Avignon and the other in Rome. The German secular and spiritual leaders voiced their support for the successor in Rome, which had far-reaching consequences for the German students and teachers in Paris: they lost their stipends and had to leave.

Rupert I recognized the opportunity and initiated talks with the Curia, which ultimately lead to a Papal Bull for foundation of a university. After having received in 1385 the permission from pope Urban VI to create a school of general studies, the final decision to found the university was taken in June of 1386 at the behest of Rupert I, Count Palatine of the Rhine. As specified in the papal charter, the university was modeled after University of Paris and included four faculties: philosophy, theology, jurisprudence, and medicine.

A special Pontifical High Mass in the Heiliggeistkirche was the ceremony that established the university. On October 19, 1386, the first lecture was held, making Heidelberg the oldest university in Germany. Today the university consists of twelve faculties and offers degree programs at undergraduate, graduate and postdoctoral levels in some 100 disciplines. The university's noted alumni include eleven domestic and foreign Heads of State or Heads of Government.