Patroclus was born in Opus, the chief city of Locris in central Greece, the son of Menoetius, the king of that city, and his wife Sthenele or Philomela or Periopis, depending on which poet tells the tale. His father was a son of Actor, the king of Opus, and his mother was a descendant of one of the great houses of the region. As a boy, Patroclus was high-spirited and quick-tempered, and during a game of dice or knucklebones in the palace courtyard, he struck a companion named Clysonymus or Clesonymus in a fit of childish rage and killed him. The death was accidental, but it was murder nonetheless, and Menoetius, fearing the blood-feud that would follow, sent his son into exile. The boy travelled to Phthia, the kingdom of Peleus in Thessaly, and there he was received into the household as a companion for Peleus's son Achilles, who was of an age with him. The two boys became inseparable, and their friendship, which would last until death, was formed in the wrestling grounds and the hunting fields of Phthia.

When the Trojan War began, Patroclus sailed with Achilles and the Myrmidons, the fierce warrior tribe of Phthia, to the muster at Aulis and thence to Troy. He was not merely a squire or a servant, though he did serve as Achilles's charioteer, driving the war-car that carried the hero into battle. He was Achilles's closest friend, the man who shared his tent, his table, and his confidence, and the only person who could speak to the hero without fear of his terrible temper. The Greeks said that Patroclus was older than Achilles, or that he was younger, or that they were of an age; what mattered was that their bond was closer than brotherhood, a friendship so absolute that the loss of one would destroy the other. In the Iliad, Achilles calls Patroclus the man he honoured above all others, the dearest of his companions, and the grief that follows his death is the most terrible in all Greek literature.

The crisis came in the ninth year of the war, when Agamemnon, the high king of the Greeks, insulted Achilles by seizing his war-prize, the slave-girl Briseis, and Achilles withdrew from the fighting in a rage. Without Achilles, the Greeks were driven back to their ships, and the Trojans, led by Hector, the greatest warrior on the Trojan side, broke through the wall that protected the Greek camp and set fire to the vessels. Patroclus watched the destruction with horror, and he went to Achilles and begged him to return to battle. Achilles refused, still burning with pride and anger, but he agreed to a compromise: Patroclus could wear Achilles's divine armour, forged by Hephaestus, the smith-god, and lead the Myrmidons into battle in his place. The plan was meant to terrify the Trojans with the appearance of Achilles without risking the hero himself, but Patroclus, once he was in the armour and at the head of the army, was carried away by the fury of battle.

He drove the Trojans back from the ships, killing Sarpedon, the Lycian prince and son of Zeus, in single combat. He pressed on toward the walls of Troy itself, forgetting Achilles's warning not to pursue the enemy too far. Apollo, the god of light, who favoured the Trojans, struck the helmet from Patroclus's head and shattered his spear. Euphorbus, a Trojan warrior, wounded him in the back with a spear, and then Hector, the Trojan prince, delivered the fatal blow, driving his spear through Patroclus's belly. As Patroclus died, he prophesied that Hector would not live long, for Achilles would avenge him, and Hector, knowing the prophecy was true, stripped the divine armour from the body and wore it himself.

Achilles received the news and his grief was absolute. He lay upon the earth and covered himself with dust, tearing his hair and screaming Patroclus's name until the sound reached the ears of Thetis, his mother, in the depths of the sea. He refused to eat, to sleep, or to wash until he had avenged his friend, and his rage was so terrible that even the gods feared it. He returned to battle, forged a new armour by Hephaestus, and killed Hector in single combat before the walls of Troy. But vengeance was not enough. Achilles dragged Hector's body behind his chariot around the tomb of Patroclus for twelve days, defiling the corpse in a frenzy of grief that only the intervention of the gods could end. He held funeral games for Patroclus that lasted nine days, with contests in chariot-racing, boxing, wrestling, and running, and he sacrificed twelve Trojan captives upon the pyre, a horror that even the Greeks who sang the story found hard to justify. When the pyre burned down, Achilles gathered Patroclus's bones and placed them in a golden urn, vowing that his own bones would one day rest beside them. The vow was kept: when Achilles died, his ashes were mingled with those of Patroclus in the same urn, and the two friends were buried together at the Hellespont.