Historically, Thespiae figures chiefly as an enemy of Thebes. During the Persian invasion of 480 BC it was one of the few cities in Boeotia to reject the example set by the Thebans, sending seven hundred men with Leonidas to Thermopylae. After the city was burned down by Xerxes I, the remaining inhabitants furnished a force of 1800 men to the confederate Greek army at Plataea. During the Athenian invasion of Boeotia in 424, the Thespian contingent of the Boeotian army sustained heavy losses at the battle of Delium, and in the next year the Thebans took advantage of this temporary enfeeblement to accuse their neighbors of friendship towards Athens and to dismantle their walls. In 414 they interfered again to suppress a democratic rising. In the Corinthian war Thespiae sided with Sparta, and between 379 and 372 repeatedly served the Spartans as a base against Thebes. In the latter year they were reduced by the Thebans and compelled to send a contingent to the Battle of Leuctra in 371. It was probably shortly after this battle that the Thebans used their new predominance to destroy Thespiae and drive its people into exile. The town was rebuilt at some later time. In 171, true to its policy of opposing Thebes, it sought the friendship of Rome. It is subsequently mentioned by Strabo as a place of some size, and by Pliny as a free city.
Although citizens of Thespiae are called Thespians, the common word thespian meaning an actor comes not from this city but from the legendary first actor, Thespis.