King Acrisius of Argos, warned by Delphi that his grandson would kill him, locked his daughter Danaë in a bronze chamber. Zeus visited her as a shower of gold, and she bore Perseus. Unwilling to kill Zeus's child, Acrisius cast mother and infant to sea in a chest; they washed ashore on Seriphos, where the fisherman Dictys raised the boy. Dictys's brother Polydectes, king of the island, later lusted after Danaë and sought to remove Perseus by demanding Medusa's head as a gift.

Hermes and Athena armed Perseus with winged sandals, a harpe, Hades's helm of invisibility, a kibisis for the head, and a polished shield in which to view Medusa safely. After forcing the Graeae to reveal the Gorgons' lair, he beheaded the mortal Medusa while she slept; from her neck sprang Pegasus and Chrysaor. Returning, he used the still-potent head to petrify foes, including — in some tellings — Atlas.

In Aethiopia he found Andromeda chained as a sacrifice to Cetus after her mother Cassiopeia's boast offended the Nereids. Perseus slew the monster, married Andromeda despite her betrothed Phineus (whom he petrified), and on Seriphos turned Polydectes to stone, making Dictys king. He gave Medusa's head to Athena for her aegis.

The oracle was fulfilled when Perseus accidentally killed Acrisius with a discus or quoit at games in Larissa. Ashamed to take Argos by bloodshed, he exchanged kingdoms with Megapenthes and ruled from Tiryns; Pausanias and others credit him with founding or fortifying Mycenae. With Andromeda he fathered Perses (left as ancestor of the Persians in Greek lore), Alcaeus, Electryon, Sthenelus, Gorgophone, and others — the Perseid line that leads to Alcmene and Heracles.

Greek tradition treated Perseus as a quasi-historical figure; Pausanias notes a roadside shrine between Mycenae and Argos and a sacred fountain Persea at Mycenae. The hero and Andromeda were also placed among the constellations.