In epic tradition, the hero Achilles besieged Methymna during the time of the Trojan War, and was assisted by the Methymnian princess Pisidice who opened the city gates in exchange for him marrying her.

The story of Arion and the dolphin, which involves the Corinthian tyrant Periander and is evidently set at the turn of the 7th century BCE, suggests that Methymna was already a prominent city with far-reaching contacts across the Greek world at this period.

[8] However, another local historian, Hellanicus of Lesbos, writing in the mid-5th century BCE, instead simply says Assos was an Aeolian foundation and does not specify a particular city as its founder.

[13] Methymna was briefly captured by the Spartans in summer 412, before quickly being retaken by the Athenians: in describing this episode, the historian Thucydides indicates that the Methymnaeans were much more inclined to side with Athens than Sparta.

[14] This was likewise the case in 411, when a group of Methymnaeans who were in exile at Cyme in Aeolis attempted to return to Methymna by force, but were rebuffed by the population.

[15] When the Spartan commander Kallikratidas besieged Methymna in 406, the city stayed loyal to its Athenian garrison and held out until it was betrayed by several traitors.

[16] Our knowledge of the history of Methymna in the 4th century is limited, but its prominence as a polis is firmly attested by the city's silver and bronze coinage.

[19] The political history of the following four years are poorly attested: we know that Lesbos changed hands several times between the Macedonian forces of Alexander the Great and the Persian forces of Memnon of Rhodes, that Memnon captured Methymna in 333 BCE, and that when Alexander's admiral Hegelochus recaptured Methymna in 332 BCE its tyrant was Aristonicus not Kleommis.

Whatever the case, in 332 Alexander gave Aristonicus over to the newly restored Methymnaean democracy to try, and he was found guilty and put to death by torture.

[24] Worship of Sarapis, an Egyptian cult patronized by the Ptolemies, was probably introduced to Methymna at this period, and remained an important part of the city's life for several centuries.

[32] We also learn from Horace that Methymnaean grapes were equally prized for the excellent vinegar which could be produced from them and which he describes accompanying a sumptuous eel dish.

[33] The medical writer Galen, who was a native of nearby Pergamon, considered all the wines of Lesbos to be excellent, but ranked that of Methymna the first in quality, that of Eresos second, and that of Mytilene third.

[36] In 640, Methymna was mentioned in the Ecthesis, pseudographically attributed to Epiphanius of Salamis, as an autocephalous archdiocese, and around 1084, it was made a metropolitan see under Alexius I Comnenus.