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As the play begins, the invading army of Argos has been driven from Thebes, but in the course of the battle, two sons of Oedipus (Eteocles and Polynices) have died fighting for opposing sides. Their uncle, Creon, is now king of Thebes. He decrees that the body of Polynices, who fought against his native city, will not be given burial rites but will be left to rot, as a warning to traitors. Creon further decrees that anyone who does try to bury Polynices will be punished with death.

Oedipus's daughters, Antigone and Ismene, are grieving for the loss of their two brothers, but Antigone is also defiant. She declares that the burial traditions are the unwritten laws of the gods, and are more important than the decrees of one man. She vows to give Polynices the proper burial rites. Ismene begs Antigone not defy the laws of the city and add to their family's tragedy. Antigone will not yield.

Antigone is caught in the act of performing funereal rites for her brother. Creon is furious, and has Antigone brought before him. She remains defiant, and says that she will not break the laws of the gods just to follow Creon's unjust law. Creon responds that she will die for her disobedience to the laws of the city. Ismene pleads with Creon to spare her sister's life. Antigone is engaged to Creon's son, Haemon, and the two of them are very much in love. But Creon is as unyielding in his allegiance to the rule of law as Antigone is to the unwritten traditional rules of the gods.

Haemon comes to Creon to ask him to reconsider. The citizens of Thebes are sympathetic to Antigone's desire to bury her brother, but are too afraid of Creon to speak up. Creon grows angry at his son's attempt to offer him advice. Their exchange grows heated. Haemon insists he is trying to prevent his father from pursuing an injustice. Creon accuses his son of siding with a reckless traitorous woman over his own father, to whom he owes obedience. Haemon threatens that the death of Antigone will lead to another death, and then rushes away, saying that Creon will never see him again.

Antigone laments her approaching death and all that she is giving up in refusing to bend to Creon's law. Guards lead her away to be sealed up (alive) in a tomb. Tiresias, the blind prophet, warns Creon that he is about to make a terrible mistake in killing Antigone, and that he should not leave the body of Polynices unburied. Creon flies into another rage and accuses Tiresias of false prophecy and of accepting bribes. Upset, Tiresias tells Creon that as punishment for killing Antigone, the gods will soon take the life of Creon's child. Creon is shaken by this, and eventually decides to relent. He rushes off to free Antigone from the tomb.

After Creon has left, a messenger arrives at the palace with the news that Haemon has killed himself. Eurydice, Haemon's mother and Creon's wife, asks to know what happened. The messenger says that Haemon went to Antigone and found that she had hanged herself. When Creon arrived, Haemon lunged at him with his sword, then used the weapon to kill himself. Eurydice leaves without a word. Creon returns, overcome with grief, carrying the body of his son. He cries out and blames himself for driving his son to suicide. A messenger enters with the news that Eurydice has killed herself while cursing Creon for murdering their son. Creon is left a broken man.