Pyrrha is usually the daughter of Epimetheus and Pandora, and thus granddaughter of the Titan Iapetus through her father. Some accounts instead make her a daughter of Prometheus. She marries Deucalion, son of Prometheus, and by him has three sons — Hellen, Amphictyon, and Orestheus — and three daughters — Protogeneia, Pandora, and Thyia. Some accounts credit Hellen (or Helmetheus) instead to a union of Pyrrha with Zeus.

When Zeus resolves to end the Bronze Age with a deluge, Prometheus — though imprisoned — foresees the flood and warns Deucalion to build an ark. Pyrrha and Deucalion alone survive; they land on Mount Parnassus, the only place spared. After the waters subside, Deucalion consults the oracle of Themis about how to repopulate the earth and is told to throw the bones of his mother behind his shoulder.

They understand the "mother" to be Gaia and the "bones" to be rocks. The stones thrown by Pyrrha become women; those thrown by Deucalion become men. The motif of stones becoming people after the flood is first attested in the sixth-century BC logographer Acusilaus, who may have played on the similarity of Greek words for "stone" and "people."

Ovid's Metamorphoses retells the story at length: Jove pities the devout couple, parts the clouds, and ends the deluge. When Themis tells Pyrrha to cast her mother's bones, she recoils at the seeming desecration until Deucalion reasons that the goddess means Mother Earth. Ovid then digresses on heat and moisture as the sources of life.

In historical times travelers at Cynos were shown Pyrrha's grave. Strabo says all of Thessaly was once called Pyrrhaea in her honour, and two small islands off Phthiotis were named Pyrrha and Deucalion. The myth inspired modern plays, operas, and artworks, and the asteroid (632) Pyrrha was named for her.