Glaucus was born a mortal in Anthedon, a city on the coast of Boeotia in central Greece, overlooking the Euboean Gulf. His father was named variously as Copeus, Polybus, or Anthedon himself, and in some accounts he was said to be the son of Poseidon, the god of the sea, or of Nereus, the gentle Old Man of the Sea who knew all the secrets of the deep. He made his living as a fisherman, casting his nets and lines into the waters that would one day become his home. One day, after a successful catch, he laid his fish upon a patch of strange grass that grew near the shore. To his astonishment, the fish began to twitch and revive, leaping from the grass back into the sea as if they had never been caught. Glaucus tasted the herb himself, and instantly an irresistible longing for the sea overcame him. He plunged into the waves and never returned to dry land. The herb, which some said had been sown by Cronus, the Titan father of Zeus, and used by Helios, the sun god, as feed for his chariot horses, had made him immortal. But immortality came at a price: his legs fused into a shimmering fish's tail, his hair turned sea-green, and his shoulders broadened into a form that was neither fully human nor fully fish.

The sea deities Oceanus and Tethys, the primordial Titans who embodied the rivers and the sea, received him kindly, and he was accepted among the gods of the deep. He became a companion of the Nereids, the fifty sea nymphs who danced on the waves and guided sailors through storms, and he learned from them the art of prophecy. His oracles were so highly regarded that fishermen and sailors watched for his annual visits, when he would travel to every coast and island of Greece to deliver his prophecies in person. The scholiast on Apollonius of Rhodes records that his prophetic power was said to be even greater than that of Apollo, the Olympian god of prophecy, who was called his disciple in the art. Aristotle wrote that he dwelt on the island of Delos, where he gave oracles in conjunction with the nymphs, and Pausanias records that the people of Anthedon still showed the place where he had dived into the sea.

In one tradition, recorded by Athenaeus and the mythographer Possis of Magnesia, Glaucus was not merely a fisherman but the builder and pilot of the Argo, the ship that carried Jason and the fifty heroes on their quest for the Golden Fleece. During a sea battle between the Argonauts and the Etruscans, he fell overboard and sank to the bottom of the sea, where by the will of Zeus he was transformed into a sea god. In this version, he had already been a hero before he became immortal, and his transformation was a reward for his service rather than an accident of curiosity. In yet another version, recorded by Nicander and cited by Athenaeus, Glaucus was chasing a hare on Mount Oreia when the animal fell nearly dead. He rubbed it with a bunch of grass that revived it, then tasted the grass himself and fell into a state of divine madness, during which Zeus made him fling himself into the stormy sea. However he came to the water, he became one of its powers, a protector of sailors and fishermen who used his immortality to rescue those washed overboard and to guide ships through dangerous waters.

The most famous episode of Glaucus's immortal life was his love for Scylla, a beautiful sea nymph who played in the waters near the shore. Glaucus saw her and was instantly captivated, but when he approached her she fled in terror at the sight of his fish-tail and sea-green hair. Heartbroken, he went to the sorceress Circe, the witch-goddess who lived on the island of Aeaea, and begged her for a potion that would make Scylla love him. Circe, however, had herself fallen in love with Glaucus. When he rejected her advances and declared that his heart belonged to Scylla alone, Circe's jealousy turned to rage. She could not harm Glaucus, for she loved him too well, so she turned her magic upon the nymph instead. She poisoned the waters of the little bay where Scylla bathed, sprinkling them with herbs of ghastly juice and muttering incantations. When Scylla entered the water, dogs sprang from her thighs and she was transformed into the six-headed sea monster who would haunt the Strait of Messina and devour sailors for eternity. Glaucus wept at the sight of her transformation and fled from Circe's embrace, his love for Scylla unchanged but his beloved now a creature of horror.

Glaucus appears in other myths as well. He attempted to woo Ariadne, the Cretan princess whom Theseus had abandoned on the island of Naxos, but the god Dionysus, the god of wine and ecstasy, also desired her. The two gods parted on good terms, and Ariadne married Dionysus. Glaucus also abducted Syme, the daughter of Ialysus, the ruler of Rhodes, and took her to an uninhabited island in the South Aegean that he named after her. In some traditions he was the father of Deiphobe, the long-lived Cumaean Sibyl who guided Aeneas through the underworld in Virgil's Aeneid. Through all these adventures, he remained the friend of fishermen, the prophet of the sea, and the immortal who had once been mortal and never lost his sympathy for those who cast their nets upon the waters.