The story begins in Iolcus, a city of Thessaly associated with the Pagasaean Gulf. Jason was the son of Aeson and, in one familiar genealogy, Alcimede. Pelias, Aeson's half-brother and a son of Poseidon, held the throne. Traditions about Jason's childhood connect him with Chiron, the centaur who educated several Greek heroes. When Jason appeared before Pelias wearing only one sandal, he fulfilled an omen that the king had been warned to fear. Accounts differ over the circumstances in which the sandal was lost, but the encounter led to the demand for a distant treasure. Jason was to travel to Colchis at the eastern end of the Black Sea and bring back the Golden Fleece. This was the hide of the ram that had carried Phrixus away from danger; his sister Helle had fallen during their flight. Phrixus dedicated the fleece in Colchis, where it belonged to King Aeëtes, a son of Helios, and hung in a grove of Ares guarded by a dragon. Pelias expected the expedition to remove Jason rather than secure his return.

Jason accepted the challenge and gathered companions from across Greece. Argus built the Argo with Athena's assistance, and the goddess fitted into it a piece of the prophetic oak of Zeus at Dodona. The speaking timber gave the ship more than a human voice, although accounts differ over its precise position. The Argo's reputation as a pioneering vessel belongs to myth, not the history of shipbuilding. Apollonius of Rhodes, whose Argonautica was composed in the third century BCE, gives a long catalogue rather than a crew list shared by every ancient author. Heracles, Orpheus, Castor and Polydeuces, Peleus, Telamon and Meleager stand beside specialists such as Tiphys the helmsman and Idmon the seer. Zetes and Calais, the winged sons of Boreas, bring powers no ordinary sailor possesses. In Apollonius, Atalanta wished to join but Jason refused her because he feared conflict among the men. Apollodorus, however, includes her among the assembled Argonauts. Medea joins the return voyage. Their shared voyage joins heroes with separate lineages, abilities and later adventures into a single company.

One of the first major landfalls was Lemnos, where women ruled after killing their husbands and other male relatives. Queen Hypsipyle had secretly spared her father Thoas. The Argonauts stayed with the women, and Jason became Hypsipyle's lover. Apollodorus names two sons of their union, Euneus and Nebrophonus, rather than treating those names as alternatives for one child. Heracles eventually challenged his companions to remember their mission, and the ship sailed on. Near Cyzicus, the young king of the Doliones welcomed them. In Apollonius's version, six-armed Earthborn giants then attacked the ship while some of the crew were away; Heracles and the returning companions defeated them with arrows and spears. Only after this encounter did the expedition leave and, driven back by contrary winds at night, return without recognising the coast. The Doliones mistook the newcomers for enemies. In the fighting Jason killed Cyzicus, his own host. At dawn both sides discovered the mistake, and the Argonauts mourned the king and held funeral rites. Hospitality had turned into tragedy through darkness and misrecognition.

The next great separation came at Mysia. Hylas, the young companion of Heracles, went ashore to fetch water and was drawn into a spring by a nymph or nymphs captivated by him. The accounts describe an abduction or disappearance, not simply a confirmed drowning. Polyphemus, a fellow Argonaut distinct from the Cyclops of the Odyssey, heard his cry and helped search for him. Heracles joined the search, and the Argo departed without them. Apollonius makes the departure and the argument that follows a difficult moment for the crew; the sea-god Glaucus explains that Heracles has another destiny. Losing its strongest companion forces the expedition to continue without treating strength as its only resource. Hylas's disappearance remains one of the voyage's most memorable losses, while the continuing quest shows how the company survives a change that none of its members can simply undo.

In Thrace the Argonauts encountered Phineus, the blind seer tormented by the Harpies, who snatched or befouled his food. Zetes and Calais pursued the winged creatures and freed him from their attacks. In gratitude, Phineus explained the route ahead and warned of the Symplegades, the Clashing Rocks at the entrance to the Black Sea. He told the heroes to release a dove before attempting the passage. If it survived, their ship should follow. The bird escaped with the loss of its tail feathers, and the crew rowed after it. With divine assistance the Argo passed through, losing only part of its stern ornament as the rocks closed. The passage fixed the rocks in place thereafter in the myth. Further along the route, at the island of Ares, the heroes drove away dangerous birds and met four shipwrecked sons of Phrixus. These young men were grandsons of Aeëtes, and their knowledge helped the visitors approach Colchis. Guidance, timely help and the willingness to listen were as important as the force of the oars.

The Argonauts sailed up the river Phasis into Colchis. Aeëtes received the request for the fleece with suspicion and set Jason a task: yoke fire-breathing bulls, plough a field, sow it with dragon's teeth and overcome the armed men that sprang from the ground. Jason accepted, though the challenge appeared beyond mortal strength. In Apollonius, Hera and Athena seek Aphrodite's help, and Eros makes Medea, the king's daughter, fall in love with the stranger. Medea knew the arts associated with Hecate and secretly offered Jason protection. She gave him an ointment to withstand the bulls' fire and instructed him to throw a stone among the earthborn warriors so that they would turn against one another. Jason yoked the bulls, ploughed and sowed, then used the confusion among the warriors to overcome them. The scene does not make him an unaided conqueror: Medea's knowledge and decision to help are essential. These Colchian earthborn fighters should also not be confused without explanation with the separate Theban Spartoi of Cadmus's story.

Aeëtes still intended to prevent the foreigners from leaving with the fleece. Medea led Jason to the grove, subdued the guarding dragon with her knowledge of drugs and incantations, and helped him take the treasure. They fled aboard the Argo, with Medea leaving her home and family behind. What happened to her brother Apsyrtus differs sharply between accounts. In Apollodorus, Medea takes the boy with her, kills him during Aeëtes' pursuit and scatters his remains, forcing her father to stop and gather them. In Apollonius, Apsyrtus is an adult commander pursuing the fugitives; Medea helps lure him into an ambush, and Jason kills him. These are alternative versions, not consecutive stages of one event. Both make the escape morally darker than a simple victory over a monster. The fleece is won, but the killing of a kinsman brings a demand for purification that the voyagers cannot leave behind with the Colchian shore.

The return journey was as perilous as the voyage out, and its route varies with the author. Circe, Medea's aunt, purified Jason and Medea of the blood-guilt associated with Apsyrtus. Orpheus opposed the Sirens' song with his lyre, although Butes leapt into the sea and was saved by Aphrodite. The voyage also brought the ship into the dangerous waters associated with Scylla, Charybdis and the Wandering Rocks, where Thetis and the Nereids supplied crucial help. In Apollonius, the Argonauts were stranded in the Libyan shallows and carried the Argo across land before finding their way out through the aid of Triton. Later, approaching Crete, they encountered Talos, the bronze guardian who hurled rocks to keep ships away. Apollonius describes him as a survivor of a bronze race and a gift of Zeus to Europa; other accounts connect his making with Hephaestus. Medea bewitched him, and in Apollonius he struck his vulnerable ankle against a rock while resisting the ship. His ichor escaped and he fell. Other versions describe a fastening removed from his ankle. After Crete, darkness overwhelmed the sailors, and Apollo's light revealed the island they named Anaphe. The Libyan episode and the rescue in darkness are separate adventures, not one event in a swamp. The expedition finally reached its home shore.

The aftermath belongs especially to the later stories of Jason and Medea. In Apollodorus, Jason returns with the fleece, and Medea brings about Pelias's death by persuading his daughters that they can restore his youth. Jason and Medea are then driven away and settle at Corinth. Euripides' Medea tells how Jason's proposed new marriage leads Medea to kill the Corinthian princess and her own children; other ancient traditions give different accounts of the children's deaths. The Argo also enters Jason's later fate: in Euripides, Medea predicts that a fragment of the vessel will strike and kill him. This is not part of the homecoming narrated at the end of Apollonius's epic. The original companions do not share one single ending, and the successful recovery of the fleece does not settle every conflict created by the expedition. Their voyage brings the great heroes into one company for a time, then releases them into separate lives. The quest succeeds, but its consequences continue beyond the ship's return.