Medusa was slain by the hero Perseus, a feat accomplished with divine aid, and from her severed neck sprang Pegasus and Chrysaor.

The climax of Medusa's story, consistent across most mythological tellings, is her death at the hands of the hero Perseus. Tasked by King Polydectes to bring him Medusa's head, Perseus embarked on a perilous quest, aided by several Olympian deities. Athena provided him with a highly polished bronze shield (or Aegis), Hermes lent him winged sandals and a curved sword (or adamantine sickle), and Hades contributed his Cap of Darkness, rendering him invisible. Using the reflective shield to avoid her direct gaze, Perseus approached Medusa while she slept and decapitated her. From her severed neck, two beings sprang forth: Pegasus, the winged horse, and Chrysaor, the giant who carried a golden sword. Both are often considered the children of Poseidon, conceived during his violation of Medusa, their birth from her death signifying a profound, if tragic, act of creation. Her head, still retaining its petrifying power, was later used by Perseus as a formidable weapon before being given to Athena, who affixed it to her shield or breastplate, the Aegis, as a symbol of protection.