The first ruler of Epirus to receive the title of Despot was Michael II, from his uncle Manuel of Thessalonica in the 1230s, and then again, as a sign of submission and vassalage, from the Nicaean emperor John III Vatatzes.

[3][4] Earlier historians assumed that Michael I was indeed named "Despot" by the deposed emperor Alexios III Angelos after ransoming him from Latin captivity in c. 1206/7 or c. 1210; this has been disproven by more recent research.

[6] The title of Despot did not imply any specific territorial jurisdiction, nor was it hereditary; it was merely the highest rank in the Byzantine court hierarchy, awarded by a reigning emperor to close relatives, usually his sons.

Consequently, it was often borne by the princes sent to govern semi-autonomous appanages and only later came to be associated with these territories as the practice became regularized (aside from Epirus, the Despotate of the Morea is the most notable case).

Epirus soon became the new home of many refugees from Constantinople, Thessaly, and the Peloponnese, and Michael was described as a second Noah, rescuing men from the Latin flood.

John X Kamateros, the Patriarch of Constantinople, did not consider him a legitimate successor and instead joined Theodore I Laskaris in Nicaea; Michael instead recognized the authority of Pope Innocent III over Epirus, cutting ties to the Eastern Orthodox Church.

The Latin Empire fell into disarray after losing the Battle of Poimanenon to the Nicaeans, and could not stop Theodore from capturing Thessalonica in 1224.

In 1230 Theodore broke the truce with Bulgaria, hoping to remove Ivan Asen II, who had held him back from attacking Constantinople.

Theodore's younger son Demetrios Angelos Doukas lost Thessalonica to Nicaea in 1246 and Michael II of Epirus allied with the Latins against the Nicaeans.

Michael VIII did not attempt to annex Epirus directly, and allowed Nikephoros I to succeed his father and deal with Charles, who captured Dyrrhachium in 1271.

After Nikephoros's death in c. 1297 Byzantine influence grew under his widow Anna, Andronikos's cousin, who ruled as regent for her young son Thomas I Komnenos Doukas.

He was overthrown by his brother John in 1323, who attempted to balance submission to Constantinople with cooperation with the Angevins of Naples, who also claimed Greece as part of their domains.

In 1337 the new Emperor, Andronikos III Palaiologos, arrived in northern Epirus with an army partly composed of 2,000 Turks contributed by his ally Umur of Aydın.

[15] In 1339 a revolt began, supported by Catherine of Valois, who had previously moved to the Peloponnese, and by Nikephoros who had returned to Epirus, based in Thomokastron.

[16] Nikephoros II took advantage of the Byzantine civil war and the death of Dušan (1355) to escape and to reestablish himself in Epirus in 1356, to which he also added Thessaly.

Nikephoros was killed in battle putting down an Albanian revolt in 1359, and the territory of the former despotate became a component part of the personal Empire of Dušan's brother Simeon Nemanjić-Palailogos.

In 1367 a part of the Epirotan Despotate was resurrected under local Serbian nobleman Thomas II Preljubović, who kept Ioannina.

The state tradition was carried on by the Serbian and Italian rulers of Ioannina, who solicited aid from the Ottoman Turks against the Albanians.

In 1399 the Albanian leader of Principality of Gjirokastër, Gjon Zenebishi captured the Despot Esau de' Buondelmonti and released him after 15 months, when his relatives in Italy offered a huge amount of money as a ransom.

But internal dissension eased the Ottoman conquest, which proceeded with the capture of Ioannina in 1430, Arta in 1449, Angelokastron in 1460, and finally Vonitsa in 1479.