Early in the 5th century Histiaios, tyrant of Miletus, unsuccessfully beseiged the island. In the Persian wars, despite the famous walls of their city, the Thassians submitted tamely to the invader. A dispute with Athens about the mainland mines led to the reduction of the island in 463, but in 466 Thassos seems to have taken over again the mineral works of Galepsos. From Thassos in 464 Thoucydides set out on his unsuccessful attempt to break the Spartian siege of Amphipolis. Lysander massacred its Athenian partisans in 404, but Thassos again allied with Athens in 389 and became a permanent member of the second Athenian league. About 360 the island was seized by Philip II and it remained Macedonian until the Romans arrived in 196 B.C. During this period it developed a flourishing export of wine, and Thassians merchants carried on the trade between Thrace and Southern Greece. Under the Empire Thassian marble and oil enjoyed an international reputation. The medieval history of Thassos is obscure; the capital was removed to the interior because of pirates. Before passing under Turkish domination in 1455, the island was a fief of the Genoese Gattilusi. In 1760 it was given by Mahmud II to the family of Mehmet Ali, and became in consequence in 1813-1920 a quasi-independent appanage of Egypt, having its own president. In 1770-74 it was occupied by a Russian fleet which made great inroads into the timber. In October 1912 it was occupied by the Greek army, in 1916 by the Allies, and in 1941 by Bulgars.

Thassos was the birthplace of Polygnotos, the painter, of the rhapsodist Stesimbrotos, and of Theogenes, son of Timoxenos, who said by Paysanias to have carried off no fewer than 1,400 athletic crowns. The physician Hippocrates leaved for three years in Thassos, whose climatic variations he recorded. Excavations since 1910 have been undertaken by the French School, which publishes an excellent detailed guide.