Neoptolemus was the son of Achilles and the princess Deidamia, and brother of Oneiros. Because of his descent he was sometimes called Achillides, Pelides, or Aeacides. According to Plutarch, he was the ancestor of Pyrrhus of Epirus.

Ancient writers depicted his appearance and character vividly. Malalas described him as having good stature, a good chest, a thin and white frame, a good nose, ruddy and woolly hair, and large light eyes, and as being daring, agile, and a fierce fighter. Dares the Phrygian portrayed him as large, robust, and easily irritated, with a slight lisp, a hooked nose, round eyes, and shaggy eyebrows.

Philostratus's Heroicus characterizes him as possessing a noble character, though not matching his father Achilles in greatness. He was strikingly handsome and strongly resembled Achilles, but was inferior to him in the same way that beautiful people are inferior to their statues. In the scholia to Lycophron's Alexandra, John Tzetzes notes that the term 'Skyrian dragon' refers to Neoptolemus because of his violent nature.

In the Cypria, Achilles sailed to Skyros after a failed expedition against Troy, married the princess Deidamia, and fathered Neoptolemus before being summoned back to war.

In a non-Homeric version, Achilles's mother Thetis foresaw a great war in which her son would die if he took part, so she hid him disguised as a woman at the court of King Lycomedes on Skyros. During his stay Achilles had an affair with the princess Deidamia, who bore Neoptolemus; the boy was originally called Pyrrhus after Pyrrha, the female name Achilles had used while in disguise.

Most accounts name Deidamia as his mother, though some claim Iphigenia instead, with Achilles later transporting him to Skyros after her sacrifice.

The Greeks captured the Trojan seer Helenus, who revealed three conditions for Troy's defeat: acquiring the poisonous arrows of Heracles (held by Philoctetes), stealing the Palladium, and bringing the son of Achilles into the war. Odysseus retrieved the teenage Neoptolemus from Skyros, and together they went to Lemnos to fetch Philoctetes, who years earlier had been bitten by a snake on the island of Chryse. Sophocles's play Philoctetes dramatizes this retrieval; in Philostratus's account it is Neoptolemus and Diomedes who bring Philoctetes back.

The sources portray Neoptolemus as brutal. He slew at least six men in battle and several more during the fall of Troy, including Priam, Eurypylus, Polyxena, Polites, and Astyanax. He captured Helenus and took Andromache as his concubine. When the ghost of Achilles demanded the sacrifice of Polyxena, Neoptolemus carried it out, though Euripides's Hecuba shows him conflicted and killing her painlessly.

After the war he sailed with Andromache, Helenus, and Phoenix to Epirus and became its king. By the enslaved Andromache, daughter of the Cilician king Eëtion, he fathered Molossos, Pielus, Pergamus, and Amphialus; Molossos was reckoned an ancestor of Olympias, the mother of Alexander the Great. By Lanassa, a granddaughter of Heracles, he fathered eight children.

Two accounts describe Neoptolemus's death: he was killed either after attempting to take Hermione from Orestes, or after denouncing Apollo, the god responsible for his father's death. In the first case Orestes killed him; in the second, the Delphic priest Machaereus took revenge. In some versions Pylades aided Orestes. Hyginus records that Neoptolemus, hearing his betrothed Hermione had been given to Orestes, went to Lacedaemon to demand her from Menelaus, who retrieved her and gave her to Neoptolemus; the insulted Orestes then slew him while he sacrificed at Delphi and scattered his bones across Ambracia in Epirus. The phrase 'Punishment of Neoptolemus' describes retribution in which a person suffers the same wrong he once inflicted on another, since Neoptolemus killed Priam at an altar and later died at an altar himself.

After his death his kingdom was partitioned. According to Virgil's Aeneid, Helenus, a son of Priam who later married Andromache, succeeded to the throne and bed of Pyrrhus and reigned over the Greek cities of Epirus. Tradition also holds that Myrmidons led by Neoptolemus founded Byllis in Illyria, and Stephanus of Byzantium states that the Thessalian tribe of the Ethnestae took its name from Ethnestus, one of Neoptolemus's sons, according to Rhianus's lost Thessalika.

Pausanias reports that the Delphians preserved the hearth where Neoptolemus was believed to have been killed, displaying it near the Temple of Apollo, and identified a nearby grave as his tomb. He was honored as a hero at Delphi with annual sacrifices.

Cicero's De Oratore cites Neoptolemus as a man who gained his name through deeds: originally Pyrrhus, he became Neoptolemus at Troy. Cicero also draws on Neoptolemus as portrayed in Ennius's tragedy to argue that orators should engage philosophy in moderation, gaining insight without becoming professional philosophers, using him as an example of practical action over abstract theorizing.

In the visual arts, Polygnotus's lost wall painting at Delphi, described by Pausanias, depicted post-Trojan War scenes that included Neoptolemus among its figures. He appears as a main character in Sophocles's Philoctetes, while Euripides's Andromache describes (though does not stage) his death at Delphi, and he is mentioned in Euripides's Trojan Women and Hecuba. Two hymns in the Greek Anthology mention him, one calling him the 'sacker of Troy' and 'saviour of the Greeks.'

Later literary appearances span Apollodorus's Library, Tryphiodorus's The Sack of Troy, Virgil's Aeneid, Seneca's Trojan Women, and Quintus of Smyrna's Posthomerica, as well as medieval and modern works including Gower's Confessio Amantis, Marlowe's Dido, Shakespeare's Hamlet, Racine's Andromaque, Rossini's opera Ermione, and modern novels by Mark Merlis, Colleen McCullough, Madeline Miller, and Pat Barker.