The play tells the story of the revenge of a woman betrayed by her husband. All of the action of the play is at Corinth, where Jason has brought Medea after the adventures of the Golden Fleece. He has now left her in order to marry Glauce, the daughter of King Creon. (Glauce is also known in Latin works as Creusa — see Seneca the Younger's Medea and Propertius 2.16.30. This King Creon is not to be confused with King Creon of Thebes.) The play opens with Medea grieving over her loss and with her elderly nurse fearing what she might do to herself or her children.
Creon, also fearing what Medea might do, arrives determined to send Medea into exile. Medea pleads for one day's delay, and Creon begrudgingly acquiesces. In the next scene Jason arrives to confront her and explain himself. He believes he could not pass up the opportunity to marry a royal princess, as Medea is only a barbarian woman, but hopes to someday join the two families and keep Medea as his mistress. Medea, and the chorus of Corinthian women, do not believe him. She reminds him that she left her own people for him ("I am the mother of your children. Whither can I fly, since all Greece hates the barbarian?"), and that she saved him and slew the dragon. Jason promises to support her after his new marriage, but Medea spurns him: "Marry the maid if thou wilt; perchance full soon thou mayst rue thy nuptials."
Next Medea is visited by Aegeus, King of Athens; he is aggrieved by his lack of children, and does not understand the oracle that was supposed to give him guidance. Medea begs him to protect her, in return for her helping his wife conceive a child. Aegeus does not know what Medea is going to do in Corinth, but promises to give her refuge in any case, provided she can escape to Athens.
Medea then returns to her plotting how she may kill Creon and Glauce. She decides to poison some golden robes (a family heirloom and gift from the sun god), in hopes that the bride will not be able to resist wearing them, and consequently be poisoned. Medea resolves to kill her own children as well, not because the children have done anything wrong, but because she feels it is the best way to hurt Jason. She calls for Jason once more, falsely apologizes to him, and sends the poisoned robes with her children as the gift-bearers.
Forgive what I said in anger! I will yield to the decree, and only beg one favor, that my children may stay. They shall take to the princess a costly robe and a golden crown, and pray for her protection.
The request is granted and the gifts are accepted. Offstage, while Medea ponders her actions, Glauce is killed by the poisoned dress, and Creon is also killed by the poison while attempting to save her. These events are related by a messenger.

Alas! The bride had died in horrible agony; for no sooner had she put on Medea's gifts than a devouring poison consumed her limbs as with fire, and in his endeavor to save his daughter the old father died too.
Medea is pleased with her revenge thus far, but resolves to carry it further: to utterly destroy Jason's plans for a new family, she will kill her own sons. She rushes offstage with a knife to kill her children. As the chorus laments her decision, the children are heard screaming. Jason rushes to the scene to punish her for the murder of Glauce and learns that his children too have been killed. Medea then appears above the stage in the chariot of the sun god Helios; this was probably accomplished using the mechane device usually reserved for the appearance of a god or goddess. She confronts Jason, reveling in his pain at being unable to ever hold his children again:
"I do not leave my children's bodies with thee; I take them with me that I may bury them in Hera's precinct. And for thee, who didst me all that evil, I prophesy an evil doom."
She escapes to Athens with the bodies. The chorus is left contemplating the will of Zeus in Medea's actions:
Manifold are thy shapings, Providence!
Many a hopeless matter gods arrange.
What we expected never came to pass,
What we did not expect the gods brought to bear;
So have things gone, this whole experience through!