Greeks in Malta have a long presence in Malta, which may lead back to ancient times. The archipelago was intensely Hellenized beginning in the 3rd century BC, a process which intertwined with the Christianization of Malta after the 1st century AD. The Byzantine presence was overturned by the Arab conquest of 870, and the surviving Greek community was Islamified. Maltese Christianity of the Byzantine Rite was only preserved in some parts of the country, being especially important in Gozo. These groups formed the basis for a local branch of the Eastern Orthodox Church, revived following Norman conquest in the 1120s. Although marginalized by Catholicism, which became the dominant faith, a Greek-speaking Eastern Orthodox community survived into the 15th century.

Iacob Heraclid, born Basilicò and also known as Iacobus Heraclides, Heraclid Despotul, or Despot Vodă, was a Greek Maltese soldier, adventurer and intellectual, who reigned as Prince of Moldavia from November 1561 to November 1563. He is remembered as a pioneer of the Protestant faith in Eastern Europe, a champion of Renaissance humanism, and a founder of academic life in Moldavia. Active within the Greek diaspora in several countries, he was a student of Hermodorus Lestarchus, and worked as a scribe alongside his cousin, Iakobos Diassorinos. Heraclid forged his genealogy several times, claiming to be a member of the Branković dynasty; he was more reliably related to the Byzantine nobility in Rhodes, and claimed the titular lordship of Samos. In the late 1540s and early '50s, he studied medicine at the University of Montpellier, and married a local. A duelist and alleged infanticide, Heraclid fled over the border with the Holy Roman Empire before he could be executed for murder. He was slowly won over by the Reformation, serving the Protestant princes of the Upper Saxon Circle.