In historical times it belonged to the Ozolian Locrians; but about 455 BC, in spite of a partial resettlement with Locrians of Opus, it fell to the Athenians, who peopled it with Messenian refugees and made it their chief naval station in western Greece during the Peloponnesian war. Two major battles were fought at this location. In 404 it was restored to the Locrians, who subsequently lost it to the Achaeans, but recovered it through Epaminondas.

Philip II of Macedon gave Naupactus to the Aetolians, who held it till 191 BC, when after an obstinate siege it was surrendered to the Romans. It was still flourishing about 170, but in Justinian I's reign was destroyed by an earthquake. It was again destroyed by earthquakes in 553 and in the 8th century and so on. In the Middle Ages it fell into the hands of the Venetians, who fortified it so strongly that in 1477 it successfully resisted a four month's siege by a Turkish army thirty thousand strong; in 1499, however, it was taken by Beyazid II. The mouth of the Gulf of Lepanto was the scene of the great sea fight in which the naval power of the Ottoman Empire was nearly completely destroyed by the united papal, Spanish, Habsburg and Venetian forces (Battle of Lepanto, October 7, 1571). In 1678 it was recaptured by the Venetians, but was again restored in 1699, by the treaty of Karlowitz to the Ottomans; in the war of independence it finally became Greek once more (March 1829).