King Athamus tires of his first wife, Nephele, and takes another, named Ino, a princess of Thebes. Ino wants to get rid of the children of her husband's first marriage, Phrixus and Helle, so that her own children will be heirs to the throne, but Hermes saves them by sending a flying golden ram to carry them away. Helle falls off the ram and drowns in the ocean, but Phrixus makes it safely to Colchis, where he sacrifices the ram to the gods and makes a gift of its fleece to Aetes, king of Colchis. Aetes gives Phrixus one of his daughters in marriage.

In addition, Phrixus's uncle, a king in Greece, lost his kingdom, Iolcos, to his nephew, Pelias. Jason, the king's son, had been secreted away in safety when he was young. Pelias, meanwhile, has been told by an oracle that he would die at the hands of his kinsman and to beware of anyone wearing a single sandal. This man is Jason, and he comes to reclaim his father's throne from his cousin, though Pelias says that he must retrieve the Golden Fleece first. Many great men agree to accompany Jason on this voyage.

First, they stop at Lemnos, an island of women. Next, they have a run-in with the Harpies, saving Phineas, an old man, from an unjust punishment. Then, they must pass through the Clashing Rocks and avoid the Amazons. Soon, they reach Colchis, where Cupid compels Medea, King Aetes's daughter, to fall in love with Jason (at Hera's request). The heroes are welcomed until they explain to Aetes why they have come, and so Aetes makes Jason complete dangerous tasks in order to win the Golden Fleece, hoping he will die instead. Medea knows that they are designed to kill Jason, and so she helps him, betraying her own father. Jason flees with the fleece, and Medea goes with him. Her father follows fast in their wake, and so she murders her own brother, throwing his pieces into the sea so that her father will be compelled to stop and collect them.

When they return to Iolcos, Jason finds that Pelias had forced Jason's father to kill himself and Jason's mother had died of grief. Medea devised a punishment for him whereby his own daughters would tear him apart (believing that he would be reborn of the pieces as a younger and healthier man). Jason soon decides that he would prefer to marry someone else, and so he banishes her; in recompense, she murders both his new bride and the children Medea herself has had with Jason. She escapes in a chariot drawn by dragons.