Andromache was born in Thebe Hypoplacia, the Cilician Thebe that lay beneath the wooded slopes of Mount Placus in Asia Minor. Her father was Eetion, a king rich in gold and bronze, and her mother was a queen whose name the poets did not preserve. She had seven brothers. When the Trojan War was in its ninth year, Achilles, the greatest of the Greek warriors, led a raid against Thebe. He killed King Eetion and all seven of his sons in a single day, burned the city to the ground, and carried off its treasures. He did not despoil Eetion's body but burned it in its armour and raised a barrow over the ashes, a rare act of respect from a man who would later drag Hector's corpse behind his chariot. The mountain nymphs planted elms around the tomb. Andromache's mother was taken captive and ransomed for a great sum, but she died of sickness in Troy before she could return home, struck down by Artemis, the archer-goddess of the hunt. Andromache arrived in Troy a princess without a kingdom, a bride without a family, and was given in marriage to Hector, the eldest son of King Priam and the mightiest defender of the city.

The marriage was a love match rare in Greek epic. Andromache bore Hector a son they named Scamandrius after the river that flowed past Troy, though the people called the boy Astyanax, "lord of the city," because his father alone stood between the Trojans and destruction. The most famous scene in all their life together came in the sixth book of the Iliad, when Hector returned to the city to arrange a sacrifice to Athena and found Andromache waiting for him at the Skaian Gates with their son in her arms and a nurse beside her. She took his hand and wept. She told him that Achilles had destroyed her world, that her father and brothers were dead and her mother gone, and that Hector was now her father, her mother, her brother, and her husband all at once. She begged him not to go back to the plain. She pointed to the wild fig tree where the wall was thinnest and where Agamemnon, Diomedes, and Ajax pressed their attack. She asked him to stay and guard that post. Hector smiled at his son, who shrank back from the horsehair crest on his helmet until the father laid it on the ground and kissed the boy. Then he told Andromache what every hero in Greek myth must tell the woman who loves him: he could not hide like a coward. His honour would not allow it. He would rather die fighting than live with shame. He reached for his helmet, the boy laughed, and Hector walked back through the gates to his death.

When that death came, Andromache was weaving in her chamber, preparing a warm bath for Hector's return. She heard the wailing from the walls before any messenger reached her. Her knees shook, the shuttle fell from her hand, and darkness covered her eyes. She rushed to the tower and saw Achilles dragging Hector's body behind his chariot, the dust rising around the corpse of the man who had been her whole world. Her lament in the twenty-fourth book of the Iliad is one of the most devastating passages in ancient literature. She did not mourn only her husband. She mourned her son, knowing that without Hector's protection the Greeks would kill Astyanax. She mourned herself, knowing that she would be carried off to Greece as a slave. She mourned the city, knowing that with Hector dead the walls would fall. Every fear she voiced came true.

After the Greeks sacked Troy, Andromache was allotted to Neoptolemus, the son of Achilles, as a war prize. The same man whose father had killed her family now owned her body. She bore him at least one son named Molossus, and possibly others. Neoptolemus took her back to Phthia in Thessaly, the kingdom of his grandfather Peleus, and there he married Hermione, the daughter of Menelaus and Helen of Sparta. Hermione had been betrothed to Orestes before the war, and her marriage to Neoptolemus was a political arrangement that left her bitter and jealous. She hated Andromache for bearing Neoptolemus a son while she remained childless, and she plotted with her father Menelaus to murder Andromache and Molossus. Menelaus tricked Andromache into leaving the sanctuary of Thetis where she had taken refuge, but Peleus, the aged father of Achilles, arrived in time to save her and the boy. He drove Menelaus from the land with words of contempt.

The end of Andromache's captivity came at Delphi. Neoptolemus had gone there to demand apology from Apollo for the death of his father Achilles, or in some tellings to consult the oracle about his childlessness with Hermione. Orestes, the son of Agamemnon and the former betrothed of Hermione, arranged for assassins to strike Neoptolemus down at the altar. He died, and Hermione fled with Orestes. Andromache was free. But freedom for a Trojan widow meant not a return to her lost city but a new marriage. Helenus, the Trojan seer and brother of Hector, had also been taken from Troy by Neoptolemus. When Neoptolemus died, Helenus inherited part of his kingdom in Epirus. He married Andromache, and together they built a new life on the shores of the Adriatic.

In Virgil's Aeneid, the Trojan hero Aeneas, wandering after the fall of Troy, came to Buthrotum in Epirus and found Andromache living with Helenus in a city that was a miniature copy of Troy. She had built a tomb for Hector on a mound of green turf, with twin altars where she poured offerings and wept each year. She had named a stream the Simois after the river of Troy. She had recreated the Skaian Gates in miniature. When she saw Aeneas approaching with Trojan arms, she thought he was a ghost. She asked if Hector was with him. She wept for Astyanax, telling Aeneas that her lost son would have been the same age as Aeneas' son Ascanius. Then she loaded Ascanius with gifts from her loom and told him to take them as last tokens from his kin. Aeneas called their city "a Troy in spirit" and prayed that the bond between their peoples would last for generations. Andromache's "little Troy" had no future, only a past to mourn, but her descendants would rule Molossia for centuries, and one of them, Olympias, would become the mother of Alexander the Great.