Some classical references describe her as one of three Gorgon sisters. Medusa, Stheno, and Euryale were monsters with brass hands, sharp fangs and hair of living, venomous serpents. The Gorgons and their other sisters the Graeae (and possibly the Hesperides) were daughters of Phorcys and Ceto.

In the most well known version of the myth, Medusa originally started out as a beautiful human. She was raped by Poseidon in Athena's temple. Poseidon was an arch-rival of Athena's since at one time he vied for patronage of Athens; the soon-to-become Athenians chose Athena's offering of the olive tree over Poseidon's offering of horses or a spring of water.

Upon discovery of the desecration of her temple, Athena changed Medusa's form to match that of her sister Gorgons as punishment. Medusa's hair turned into snakes and her glance would turn all living creatures to stone. She was banished beyond the Hyperborean lands.

While Medusa was pregnant by Poseidon, she was beheaded by the hero Perseus with help from Athena and Hermes. From her neck came her offspring: Pegasus and Chrysaor. Perseus used Medusa's head to rescue Andromeda, kill Polydectes, and, in some versions, petrify the Titan Atlas. Then he gave it to Athena, who placed it on her shield Aegis.