Clytemnestra was born in Sparta, the great city of the southern Peloponnese famous for its warriors and its iron discipline, the daughter of King Tyndareus and his wife Leda. Leda had been visited by Zeus, the king of the gods, in the form of a swan, and from that union came two eggs: one containing Helen and Pollux, fathered by the god, and the other containing Castor and Clytemnestra, fathered by the mortal king. Clytemnestra grew up in the palace at Sparta alongside her divine half-siblings, and when she came of age she was courted by many suitors, as was her sister Helen. Some say that both Agamemnon, king of Mycenae, and his brother Menelaus, king of Sparta, competed for the sisters' hands, with Agamemnon winning Clytemnestra and Menelaus winning Helen. Others say that Agamemnon killed Clytemnestra's first husband, a man named Tantalus, and took her by force. Either way, she became queen of Mycenae, the richest and most powerful kingdom in Greece, and bore Agamemnon four children: Iphigenia, the eldest daughter; Electra, the second daughter; Chrysothemis, the third; and Orestes, the son and heir.

The trouble began when Helen was taken from Sparta by Paris, the Trojan prince whose abduction of the queen started the war that would consume Greece for ten years. Agamemnon, as the high king who commanded the combined Greek forces, gathered his fleet at Aulis, a harbour on the coast of Boeotia, but the winds would not blow. The seer Calchas, a prophet who spoke with the voice of the gods, declared that Artemis, the goddess of the hunt and the moon, was angry with Agamemnon - some say because he had killed one of her sacred stags and boasted of his skill, others because of an old curse upon his house - and that she would not release the winds until he sacrificed his own daughter Iphigenia upon her altar. Agamemnon, desperate to sail for Troy and unwilling to lose face before the other kings, sent a message to Clytemnestra telling her that Iphigenia was to be married to Achilles, the greatest warrior of the age, and that she must bring the girl to Aulis at once. Clytemnestra, believing the wedding was genuine, dressed her daughter in bridal finery and travelled to the harbour. When she arrived, she learned the truth: there was no wedding, only a knife and an altar. She begged Agamemnon to spare the girl. She begged Achilles, who had not known his name was being used in the deception, to intervene. But the Greek army demanded the sacrifice, and Agamemnon would not relent. Iphigenia was led to the altar, and though some later stories say that Artemis replaced her with a deer at the last moment and carried her away to serve as a priestess in the distant land of Tauris, Clytemnestra believed her daughter dead, killed by her own father's hand.

Agamemnon sailed for Troy and was gone for ten years. Clytemnestra remained in Mycenae, ruling the kingdom in his absence, and during those years she took Aegisthus as her lover. Aegisthus was Agamemnon's cousin, the son of Thyestes, and he carried a blood feud of his own against the house of Atreus, for Agamemnon's father Atreus had once murdered Thyestes's children and served them to their father at a banquet. Aegisthus had been raised in exile, nursing his hatred, and now he found in Clytemnestra both a willing ally and a queen who could give him the power he craved. Together they ruled Mycenae as king and queen in all but name, and they waited.

When the war ended and Agamemnon returned, he did not come home alone. He brought with him Cassandra, the Trojan princess who was also a prophetess, cursed by Apollo so that her true prophecies would never be believed. Cassandra had seen the fall of Troy and the murder of its king Priam, and now she saw her own death and Agamemnon's as clearly as she saw the sun. Clytemnestra welcomed her husband with elaborate ceremony, spreading crimson tapestries for him to walk upon and speaking words of praise for his victory. She led him to the bathhouse, where slaves poured warm water over his travel-weary body, and there, while he was unarmed and vulnerable, she struck. In Aeschylus's telling, she threw a net or a robe over him to entangle him like a caught animal, and then struck him three times with a blade - some say an axe, some say a sword. Cassandra, who had remained outside the palace in the chariot, walked in to meet her fate and was killed as well. In Homer's earlier version, Aegisthus struck the killing blow while Clytemnestra helped, but in the great tragedies it is Clytemnestra who stands over the body and declares that she has avenged Iphigenia.

For seven or eight years, Clytemnestra and Aegisthus ruled Mycenae together. They had children of their own: a son named Aletes and two daughters, Erigone and Helen. But the curse of the house was not finished. Orestes, the son whom Clytemnestra had sent away as a child to protect him from Aegisthus's jealousy, grew to manhood in exile. The god Apollo, the Olympian deity of music, prophecy, and archery, commanded him to avenge his father's murder, and Orestes returned to Mycenae with his cousin Pylades. He killed Aegisthus first, and then, though his heart rebelled against the crime, he killed his own mother. The Erinyes, the ancient goddesses of vengeance who punish those who shed kindred blood, rose up to torment him, driving him mad across the earth until Athena, the goddess of wisdom, established the first court of law in Athens and acquitted him by a single vote. Clytemnestra's death did not end the cycle of blood. It merely passed the burden to the next generation, and the house of Atreus continued to burn.