Jason must assemble a crew of legendary heroes to retrieve the Golden Fleece from the dangerous land of Colchis. Driven by the command of King Pelias, Jason commissions the construction of the Argo, the first ship of its kind, to navigate treacherous seas. He faces divine interference, monstrous obstacles, and the internal friction of his crew, all while operating under the watchful eyes of the Olympian gods. The narrative follows a linear progression, detailing the trials of the Argonauts as they traverse the known world to secure the prize and return home.

Readers and scholars frequently highlight the poem's unique position as a bridge between the Homeric tradition and the more self-conscious literary style of the Hellenistic period. Discussion often centers on the nuanced portrayal of Medea, whose internal conflict and eventual actions provide a stark contrast to the traditional heroic archetypes of the era. Critics emphasize the balance between the expansive, adventurous scope of the voyage and the intimate, often psychological focus on the characters' motivations. Many readers appreciate how the text manages to maintain a sense of wonder while grounding the narrative in the specific cultural and historical anxieties of its time.