Samothrace was not a state of any political significance in ancient Greece, since it has no natural harbour and most of the island is too mountainous for cultivation: Mount Fengari (literally 'Mt. Moon') rises to 1,611 m (5,285 ft). It was, however, the home of the Sanctuary of the Great Gods, site of important Hellenic and pre-Hellenic religious ceremonies. Among those who visited this shrine to be initiated into the island cult were Lysander of Sparta, Philip II of Macedon and Lucius Calpurnius Piso Caesoninus, father-in-law of Julius Caesar.
The ancient city, the ruins of which are called Palaeopoli ("old city"), was situated on the north coast. Considerable remains still exist of the ancient walls, which were built in massive Cyclopean style, as well as of the Sanctuary of the Great Gods, where mysterious rites took place which were open to both slaves and free people (similar to the Eleusinian Mysteries).
The traditional account from antiquity is that Samothrace was first inhabited by Pelasgians and Carians, and later Thracians. At the end of the 6th century BC the island was colonised by Greeks from Samos.
The Persians occupied Samothrace in 508 BC, it later passed under Athenian control, and was a member of the Delian League in the 5th century BC. It was subjugated by Philip II, and from then till 168 BC it was under Macedonian suzerainty. With the battle of Pydna Samothrace became independent, a condition that ended when Vespasian absorbed the island in the Roman Empire in AD 70.
During the Roman and particularly the imperial period, thanks to the interest of the Roman emperors, the radiation of the sanctuary of the Great Gods surpassed Greek borders and Samothrace became international religious center where pilgrims flocked from all over the Roman world. Apart from the famous sanctuary, decisive role in the great development of Samothrace played also her two ports from which passed the sea road Troas - Macedonia. Furthermore, an important role played as well her possessions in Perea, which were conceded by the Romans at least during the imperial period, as evidenced by inscriptions of the 1st AD century.
The Book of Acts in the Christian Bible records that the Apostle Paul, on his second missionary journey outside of Palestine, sailed from Troas to Samothrace and spent one night there on his way to Macedonia.
The Byzantines ruled until 1204, when Venetians took their place, only to be dislodged by a Genoan family in 1355, the Gattilusi. The Ottoman Empire conquered it in 1457 and it was called Semadirek in Turkish; an insurrection against them by the local population during the Greek War of Independence (1821–1831) led to the massacre of 1,000 inhabitants. The island returned to Greek rule in 1913 following the Balkan War. It was occupied by Bulgaria during the Second World War, from 1941 to 1944.