Demophon was born in Athens, the son of Theseus, the hero who had slain the Minotaur and unified Attica, and of Phaedra, the daughter of Minos, the king of Crete. Some sources name his mother as Iope, the daughter of Iphicles, which would have made him a relative of Heracles. He had a full brother named Acamas, and half-brothers including Hippolytus, the son of Theseus and the Amazon Antiope. His early life was shadowed by tragedy. His mother Phaedra committed suicide after her false accusation of rape against Hippolytus was exposed. Then his father Theseus, having journeyed to the underworld with his friend Pirithous, returned to find that Menestheus had seized the throne of Athens in his absence. Theseus went into exile and was eventually murdered on the island of Scyros by Lycomedes, who threw him from a cliff. Demophon and Acamas, still children, were sent to Euboea, where they were raised by Elephenor, a relative by marriage who cared for them as his own.

When the Trojan War broke out, Demophon and Acamas sailed with the Greek fleet. Their personal mission was as urgent as the war itself: their grandmother Aethra, the mother of Theseus, had been captured years earlier by the Dioscuri, Castor and Polydeuces, during their raid on Athens, and had been given to Helen as a handmaiden. When Troy fell, the brothers found Aethra in the captured city and rescued her from slavery. According to the Little Iliad and Apollodorus, Demophon and Acamas were also among the warriors who hid inside the Wooden Horse, the giant hollow vessel that the Greeks left outside the walls of Troy as a supposed offering to Athena, and from which they emerged at night to open the gates and destroy the city. Aethra, however, was so heartbroken by the news of Theseus's death that she died shortly after her rescue.

The defining episode of Demophon's life took place on his journey home. His ships put in at Thrace, on the coast ruled by King Sithon, and there he met Phyllis, the king's daughter. She fell in love with him, and he married her, or in some versions betrothed himself to her with solemn oaths. The day after the wedding, he told her that he must return to Athens to settle his affairs and reclaim his father's throne. He promised to come back for her as soon as possible. Phyllis gave him a casket and told him not to open it unless he had lost all hope of returning to her. She then went to the shore every day to watch for his ship, making the journey nine times, which is why the place was later called the Ennea Odoi, the Nine Roads, and eventually Amphipolis.

Demophon never returned. Some say he was delayed in Cyprus, where he married another woman and forgot his Thracian bride. Others say he simply broke his promise. Phyllis waited until the appointed day had passed, and then she died of grief, or hanged herself, or threw herself into the sea. The gods transformed her into an almond tree, bare and leafless. When Demophon finally did return to Thrace, he found only the tree. He embraced it, and it burst into leaf and blossom, an eternal sign of love that survives death. In a darker version of the tale, Demophon opened the casket out of curiosity while in Cyprus. What he saw inside - perhaps sacred objects of the Great Mother, or a curse - was so horrifying that he leaped upon his horse and rode wildly until the terrified animal threw him, and he fell upon his own sword and died.

Demophon eventually reached Athens and succeeded Menestheus as king. His reign was marked by justice and hospitality. When the children of Heracles, the Heracleidae, were persecuted by Eurystheus, the king of Mycenae who had tormented their father with his twelve labours, Demophon gave them refuge in Athens and land to settle. Eurystheus marched against Athens, but Demophon defeated him, and the Heracleidae were saved. He also fought Diomedes, the Greek hero who had mistakenly landed in Attica and attacked its settlements, and in the battle Demophon acquired the Palladium, the sacred statue of Athena that had been taken from Troy. He established the court of the Ephetae, a tribunal of fifty-one judges that handled cases of homicide, and he himself was the first to be tried in that court, having accidentally trampled a fellow Athenian beneath his horse's hooves during the battle with Diomedes. He was acquitted. He also hosted Orestes during the period of his madness, after the prince had murdered his mother Clytemnestra to avenge his father Agamemnon. Demophon ruled for thirty-three years and died in Athens, succeeded by his son Oxyntes.