In the past the founding of Ioannina has traditionally been attributed to the Byzantine Emperor Justinian in the 6th century AD, but new archaeological research has uncovered evidence of prior Hellenistic settlements in the same area that point to its earlier existence. The settlement flourished in the late Byzantine period (XIII-XV centuries). Ioannina became part of the Despotate of Epirus following the Fourth Crusade. Many rich Byzantine families fled there following the sacking of Constantinople, in no small part due to the city’s great prosperity and considerable autonomy. In 1430 Ioannina surrendered to the Ottomans and until 1868 it was the administrative center of the Pashalik of Yanina. In the period between the XVIII-XIX centuries, the city was a major center of the modern Greek Enlightenment. In 1913 Ioannina was ceded to Greece following the Balkan Wars.
During World War II in 1940 the capture of Ioannina became one of the major aims of the Italian Army, but the Greek defense in Kalpaki pushed back the invading Italians. The city was intensively bombed by the German forces in April 1941 even during the negotiations that led to the capitulation of the Greek army. During the subsequent Axis occupation of Greece, the Jewish community in Ioannina was rounded up by the Germans in 1944.
In 1970 the University of Ioannina was funded, until then, higher education faculties in the city had been part of the Aristotle University of Thessaloniki.