Cassandra was born in Troy, the daughter of Priam, the last king of that city, and his wife Hecuba. She had a twin brother named Helenus, and together the two children were said to have received the gift of prophecy in a single night. Their parents left them to sleep in the temple of Apollo at Thymbra, near Troy, and when they returned in the morning the infants were entwined with sacred serpents that licked their ears and mouths, granting them the power to hear and speak the future. In the more famous version of the story, recorded by the tragedian Aeschylus in his play Agamemnon, Cassandra grew into a woman of extraordinary beauty and became a priestess of Apollo. The god fell in love with her and offered her the gift of prophecy in exchange for her favours. She accepted the gift, but when the time came to keep her side of the bargain she refused him. Apollo could not revoke a power he had already granted, but he could twist it. He spat into her mouth - or in some accounts simply cursed her - and ordained that no one would ever believe a word she prophesied, though every word would be true.

From that moment Cassandra lived in a private hell of perfect knowledge and perfect isolation. When her brother Paris, the Trojan prince whose abduction of Helen, the wife of Menelaus of Sparta, would spark the Trojan War, was a child, Cassandra foretold that he would bring destruction upon Troy. Her words were ignored. When Paris sailed to Greece and returned with Helen, Cassandra tried to warn her father Priam and the Trojan people that the war would end in the city's ruin. They locked her away, judging her insane. During the ten-year siege she watched the Greeks kill her brother Hector, the greatest Trojan warrior, and when his body was dragged back to the city it was Cassandra who first saw her father returning with the corpse and announced the death to the Trojan people, her voice breaking with grief.

The defining moment of her prophetic career came on the night the Greeks pretended to retreat. They left a giant wooden horse outside the walls of Troy as a supposed peace offering, and the Trojans, believing themselves victorious, debated whether to drag it inside. Cassandra rushed to the gates and told them the horse was filled with Greek soldiers who would destroy the city. She took an axe in one hand and a burning torch in the other and tried to destroy the horse herself, but the Trojans stopped her, hurling insults and calling her mad. That night the Greeks emerged from the horse, opened the gates, and Troy burned. In Virgil's Aeneid, Cassandra is described shouting her warnings in a prophetic trance, her hair crowned with laurels, while the Trojans mocked her and brought the horse within the walls.

As the city fell, Cassandra fled to the temple of Athena, the goddess of wisdom and war, and clung to the wooden statue of the goddess, begging for protection as a suppliant. But Ajax the Lesser, a Greek warrior of the Locrians, found her there. He dragged her from the statue with such violence that he knocked the image from its pedestal, and he raped her on the temple floor, a sacrilege against both the woman and the goddess. Athena was so enraged by this desecration of her sanctuary that she sent storms against the Greek fleet as it sailed home, destroying many ships. In the distribution of spoils after the fall of Troy, Cassandra fell to Agamemnon, the high king of the Greeks, who took her as his concubine and sailed with her to Mycenae. She bore him twin sons, Teledamus and Pelops, though some accounts say the children were born after their arrival in Greece.

In Aeschylus's Agamemnon, the most powerful dramatic treatment of her story, Cassandra arrives at Mycenae in Agamemnon's chariot and remains outside the palace while the king enters. She receives a series of violent visions: she sees the murder of the children of Thyestes, the ancient crime that haunts the house of Atreus; she sees Agamemnon entangled in a net and stabbed to death in his bath by his wife Clytemnestra and her lover Aegisthus; and she sees her own death at Clytemnestra's hands. She tries to warn the chorus of old men who stand watching, but they cannot understand her. In a moment of terrible clarity she accepts her fate, removes her prophetic garlands, and walks into the palace to die. Clytemnestra murders her with an axe or a blade, and in some accounts Aegisthus kills her twin sons as well. In Homer's Odyssey, the shade of Agamemnon tells Odysseus in the underworld that he heard Cassandra's death-cry as he himself was dying. Her body was buried at Amyclae or Mycenae, and her tomb became a place of reverence.