Diomedes was born in Argos, the greatest city of the Argolid, the son of Tydeus and Deipyle. His father Tydeus was one of the Seven Against Thebes, the doomed expedition of Argive heroes who attacked the city of Oedipus's sons and were destroyed almost to a man. Tydeus was a fierce warrior, small of stature but terrible in battle, and he had once defeated fifty Theban champions in single combat. But his end was gruesome. Wounded by Melanippus, Tydeus lay dying when Athena descended from Olympus with a draught of immortality to make him a god. Amphiaraus, the seer, brought her the head of Melanippus as a trophy, but Tydeus, in his final rage, split open the skull and began to eat the brains. Athena, horrified by the savagery, turned away and let him die. Diomedes grew up with this legacy: a father who had been a hair's breadth from divinity and had lost it through a moment of beastly rage.

He succeeded Adrastus as king of Argos and married Aegialia, the daughter of Adrastus or in some accounts of his son Aegialeus. When the call came to sail for Troy, Diomedes led eighty ships from Argos and Tiryns, the second-largest contingent after Agamemnon's own. He was young, strong, and already famous for his courage. On the battlefield of Troy, he distinguished himself immediately. In Book 5 of the Iliad, Homer devotes an entire book to his aristeia, his moment of supreme heroism. Diomedes fought like a demon, killing Pandarus, the Lycian archer who had broken the truce by shooting Menelaus, and wounding Aeneas, the Trojan prince and son of Aphrodite, with a stone that crushed his hip. Aphrodite came to rescue her son, and Diomedes, seeing the goddess, drove his spear through her delicate wrist. She screamed and fled to Olympus, dropping Aeneas in the dust. Apollo then came to save Aeneas, and Diomedes attacked even him, though the god warned him back with a thunderclap.

Then Ares himself entered the battle. The god of war, who had been fighting on the Trojan side, strode across the plain in his brazen armour, and Diomedes did not flinch. Athena took her place beside him, seized the whip and reins of his chariot, and gave him the strength to face a god. Diomedes cast his spear and struck Ares in the lower belly, where the war-belt crossed, a wound so terrible that the god bellowed like ten thousand men and fled to Olympus, where Zeus, the king of the gods, had him healed by Paeon, the divine physician. No mortal had ever wounded two Olympians in a single day and survived. The other Greeks looked at Diomedes with awe, and even Agamemnon, the commander of the army, treated him with new respect.

The most famous episode of Diomedes's career at Troy was the night raid. The Thracian king Rhesus had arrived with a contingent of fresh warriors and magnificent white horses, and an oracle had declared that if those horses ever smelled the grass of Troy or drank from the river Scamander, the city could never be taken. Odysseus, the cunning king of Ithaca, and Diomedes, the strongest warrior, volunteered to infiltrate the Thracian camp. Athena sent a heron as an omen, and the two heroes crept through the darkness, killed the guards, and found Rhesus sleeping in his tent. Diomedes struck him down with twelve companions, while Odysseus untethered the white horses. They drove the horses back through the Greek lines before dawn, and the oracle's condition was never met. The episode became one of the most celebrated tales of stealth and courage in the entire war.

Diomedes also exchanged armour with Glaucus, the Lycian prince, in one of the most famous scenes in the Iliad. The two warriors met on the battlefield and discovered that their grandfathers had been guest-friends, bound by the sacred laws of hospitality. They therefore could not fight each other. Instead, they exchanged armour. Glaucus gave his golden armour, worth a hundred oxen, and received Diomedes's bronze armour, worth only nine. Homer called it the exchange of gold for bronze, a hundred oxen's worth for nine, and used it as an example of how the gods can blind a man to his own advantage when they wish to destroy him.

After the fall of Troy, Diomedes's voyage home was not as troubled as those of Agamemnon or Odysseus, but it was not without incident. A storm blew him off course to the coast of Italy, where he founded the city of Argyripa, later called Arpi, in Apulia. The local people, the Daunians, received him hospitably, and he married their king's daughter. In some traditions, he continued to wander the Adriatic, founding other settlements, and eventually died of old age. But the most beautiful tradition holds that Athena, who had loved him above all mortals at Troy, granted him immortality and took him to her own island in the Adriatic, where he lived forever as a god. His wife Aegialia, meanwhile, had been unfaithful to him during his absence, seduced by Cometes or Clytius, and this betrayal may have been the reason he never returned to Argos. The Argives worshipped him as a hero after his death, and Virgil, in the Aeneid, shows the Italian settlers of Arpi fighting alongside Turnus against Aeneas, their founder's memory still potent centuries later.