During her reign, Aphrodite cursed the women of the island for having neglected her shrines. (According to Bibliotheca 1.9.17, the women were afflicted with an evil smell.) The men took up with female slaves taken on raids on Thrace. The women of the island decided upon revenge and, in one night, killed all their male relatives. Hypsipyle alone spared a male. She hid her father, Thoas, from the vengeful plan.
Soon after the androcide, Jason and the Argonauts stopped at Lemnos on their way to Colchis. The Argonauts remained on Lemnos for two summers and two winters, during that time, had extensive relations with the island's women. Jason impregnated Hypsipyle and swore eternal fidelity to her. The product of that pregnancy was twins, Euneus and Nebrophonus (or Deiphilus or Thoas). Jason, however, sailed away and quickly forgot his vows.
The Lemnian women, angry at her having spared her father, forced Hypsipyle to flee for her life. She and her sons were taken by pirates and sold to Lycurgus, king of Nemea. She was given charge of Lycurgus's son, Archemorus.
When the Argives (of Aeschylus's Seven Against Thebes or Statius' Thebaid) marched against Thebes, they met Hypsipyle and made her show them a fountain where they could get water. She set down Archemorus when she did this, and he was killed by a snake in her absence. Lycurgus wanted revenge upon Hypsipyle, but she was protected by Adrastus, the leader of the Argives.
- In his work, Inferno, the 14th-century Italian poet Dante Alighieri placed Jason in the eighth circle of Hell, along with seducers and panderers, for his deception and abandonment of Hypsipyle.