Having accidentally killed his uncle Electryon, king of Mycenae, Amphitryon was driven out by another uncle, Sthenelus. He fled with Alcmene, Electryon's daughter, to Thebes, where he was cleansed from the guilt of blood by Creon, his maternal uncle, king of Thebes.
Alcmene, who is pregnant and had been betrothed to Amphitryon by her father, refused to marry him until he had avenged the death of her brothers, all of whom except one had fallen in battle against the Taphians. It was on his return from this expedition that Electryon had been killed. Amphitryon accordingly took the field against the Taphians, accompanied by Creon, who had agreed to assist him on condition that he slew the Teumessian fox which had been sent by Dionysus to ravage the country.
The Taphians, however, remained invincible until Comaetho, the king's daughter, out of love for Amphitryon cut off her father's golden hair, the possession of which rendered him immortal. Having defeated the enemy, Amphitryon put Comaetho to death and handed over the kingdom of the Taphians to Cephalus. On his return to Thebes, he married Alcmene, who gave birth to twin sons, Iphicles being the son of Amphitryon, Heracles of Zeus, who had visited her during Amphitryon's absence.
He fell in battle against the Minyans, against whom he had undertaken an expedition, accompanied by the youthful Heracles, to deliver Thebes from a disgraceful tribute. According to Euripides in the play Hercules Furens, he survived this expedition, and was slain by his son in his madness.
John Dryden's 1690 Amphitryon is based on Molière's 1668 version as well as on Plautus. Notable innovations include music by Henry Purcell and the character of Phaedra, who flirts with Sosia but is eventually won over by Mercury’s promises of wealth. In Germany, Heinrich von Kleist's Amphitryon (1807) remains the most frequently performed version of the myth, with Kleist using Alkmene's inability to distinguish between Jupiter and her husband to explore metaphysical issues; Giselher Klebe wrote in 1961 his opera Alkmene based on this play. Other German dramatic treatments include Georg Kaiser's posthumously published Double Amphitryon (Zweimal Amphitryon, 1943) and Peter Hacks's Amphitryon (1968).
In France, the myth was the subject of a play by Jean Giraudoux, Amphitryon 38 (1929), the number in the title being Giraudoux's whimsical approximation of how many times the story had been told onstage previously. It was adapted into English by S. N. Behrman and enjoyed a successful run on Broadway in 1938. Plautus’ version was the basis of Cole Porter’s 1950 musical Out of This World.