Nicholas was the son of Count John I Orsini of Cephalonia by Maria, a daughter of Nikephoros I Komnenos Doukas of Epirus by Anna Palaiologina Kantakouzene. His father governed Cephalonia as a vassal of King Charles II of Naples, and had acquired Leukas as his wife's dowry. Nicholas succeeded to the county on his father's death in 1317, but unlike his predecessors was more interested in intervening in Epirus than in the Latin possessions in southern Greece. In 1318 he surprised and murdered his uncle Thomas I Komnenos Doukas of Epirus and easily subdued the entire southern portion of the principality around Arta. To solidify his position Nicholas also married his uncle's widow, Anna Palaiologina, daughter of Michael IX Palaiologos, and was conferred the title of despotes.
Nicholas paid nominal homage to his Angevin overlord, John of Gravina, a son of King Charles II of Naples and Maria of Hungary. He otherwise oriented himself towards the East. He publicly adopted the Orthodox faith and the local clergy raised no serious objection to his usurpation. Northern Epirus, however, with Ioannina, refused to recognize Nicholas' rule and accepted Byzantine rule. Nicholas waited until the death of his wife in 1320 or 1321 and the outbreak of the Byzantine civil war to attack. Failing in his attempt to secure an alliance with the Republic of Venice, Nicholas was unable to take Ioannina. In 1323 he was murdered by his brother John II Orsini.
|Ancestors of Nicholas Orsini|
- Cheetham, Nicholas (1981). Mediaeval Greece. Yale University Press.
- Fine, John Van Antwerp (1994). The Late Medieval Balkans: A Critical Survey from the Late Twelfth Century to the Ottoman Conquest. Ann Arbor: University of Michigan Press. ISBN 978-0-472-08260-5.
- Kazhdan, Alexander, ed. (1991). The Oxford Dictionary of Byzantium. Oxford and New York: Oxford University Press. ISBN 978-0-19-504652-6.
- Miller, William (1908). The Latins in the Levant, a History of Frankish Greece (1204–1566). New York: E.P. Dutton and Company.
- Nicol, Donald MacGillivray (2010). The Despotate of Epiros 1267–1479: A Contribution to the History of Greece in the Middle Ages. Cambridge: Cambridge University Press. ISBN 978-0-521-13089-9.
- Polemis, Demetrios I. (1968). The Doukai: A Contribution to Byzantine Prosopography. London: Athlone Press.
| Ruler of Epirus
| Count of Cephalonia