According to myth, the town of Mitilini was built by Myrina, the leader of the Amazones, as she conquered the island and named it after her sister. According to another myth, the island's first inhabitant was the son of Helios, Makaras who had five daughters: Mytilini, Methymna, Essa, Andessa and Arisve, as well as four sons: Eressos, Kydrolaos, Neandros and Lefkippus. The children named most of the island's towns after themselves. The island was offered as dowry to Lesvos, Makaras' son-in-law, named it after himself. The island of Lesvos was also mentioned in the Iliad. According to Homer, Achilleas and Aeas buried the corpse of Palamides here, a hero of the Trojan War. After the fall of the Troy, Menelaus, Diomedes and Ulysses had a conference here, to discuss their return home.

Lesvos was inhabited by the Pelasgians in 1507 BC and between 1393 and 1184 BC, it was flooded by the Achaians. 60 years after the capture of Troy, an Aeolic settlement was founded there by Gras, and in the middle of the 7th century, the Lesbians had expanded all over Troy. In 659 BC, after the assassination of the last tyrant of the Penthilides dynasty, the Lesbians constituted a great marine force which lasted for a long period of time. After a short Persian occupation (492-479 BC), they participated in the Attic-Helian League under equal conditions, but during the Peloponnesian War, they rebelled and fought together with Sparta. In 427 BC Mitilini was subjected to the wrath of the Athenians, who demolished its walls and killed 1,000 Mitilinians. In 405 BC Sparta occupied the island until 334 BC when the Lesbians made an alliance with Alexander the Great, after the death of whom the island came under the Ptolemaic rule, and in 88 BC it was conquered by the Romans. After the successive occupation by the Saracen, the Latins and the state of Nice, in 1261 it was included as part of Byzantium and during the whole Byzantine era had been used as a place of exile for eminent personalities, such as Irene the Athenian and Constantine Monomachos the 9th(the Dueller). In 1354, Lesvos was offered as a dowry to the Genoese noble Fragisco Gatelouzo, who, along with his dynasty, ruled from 1355 to1376. On 14 October 1462, the island was subjected to the forces of Moameth the Conqueror, who inaugurated the period of the Turkish rule, during which it has been used as a place of exile for eminent Turks who were out of favour with the Sultan. After the end of the Russian- Turkish war (1768-1774), the island became prosperous and started preparing the revolution against the Turks. Nevertheless, the brave revolution of the Mitilinians, in 1824, was covered with blood. In 1909, the first Lesbian members of parliament were elected, and on 8 November 1912, Mitilini was set free by admiral Kountouriotis, and after the Treaty of Athens in 1914, it was finally resigned to Greece. During the Second World War, in 1941, the island was conquered by the Germans and it was liberated finally on 10 September 1944.