Calliope was born on Mount Olympus, or perhaps on Mount Helicon in Boeotia, the mountainous region of central Greece where her sisters were said to dance around the sacred fountain of Hippocrene. Her father was Zeus, the king of the gods, and her mother was Mnemosyne, one of the elder Titans, the primordial gods who ruled before the Olympians, and the personification of memory itself. Hesiod, the poet who wrote the Theogony in the eighth or seventh century BCE, Zeus lay with Mnemosyne for nine nights in succession, and on each night she conceived a daughter. Calliope was the firstborn, the eldest of the nine Muses, followed by Clio, the Muse of history, Euterpe, the Muse of music, Thalia, the Muse of comedy, Melpomene, the Muse of tragedy, Terpsichore, the Muse of dance, Erato, the Muse of love poetry, Polyhymnia, the Muse of sacred song, and Urania, the Muse of astronomy. The sisters were tutored in the arts by their half-brother Apollo, the Olympian god of music and prophecy, and together they formed the chorus that entertained the gods on Olympus with songs of the world.

Hesiod called Calliope the chief of all the Muses, and he gave her a special role. She attended upon kings and princes, pouring sweet dew upon their tongues so that they might speak with grace and settle quarrels with gentle words. When a king passed through his assembly, the people looked upon him as a god, and this was the holy gift of Calliope. In the Classical period, when each Muse was assigned a specific art, Calliope became the Muse of epic poetry, the long narrative poems that told the deeds of heroes and the history of the gods. She was portrayed holding a writing tablet and a stylus, or in older art a lyre, the instrument that accompanied the recitation of epic verse. Poets from Homer to Virgil to Dante invoked her at the beginning of their works, asking her to inspire their words with both beauty and truth.

Calliope married Oeagrus, the mortal king of Thrace, a region in the north of Greece, in the town of Pimpleia near Mount Olympus. By him, or in some accounts by Apollo, she bore two sons who would shape the musical history of the world. The first was Linus, a musician so skilled that he was said to have been the first to pair singing with the playing of the harp, though he met a violent death at the hands of his own pupil, the hero Heracles, who struck him down in a fit of rage. The second and greater son was Orpheus, the most famous musician in all of Greek mythology. Calliope taught him to sing, and Apollo gave him a golden lyre and taught him to play. His music was so powerful that wild beasts lay down at his feet, trees tore up their roots to follow him, and even the rocks rolled along to hear his song. When his beloved wife Eurydice died of a snakebite, Orpheus descended to the underworld and sang before Hades and Persephone, the king and queen of the dead, until they wept and agreed to let her return. But he looked back too soon, and she was lost forever.

The death of Orpheus was one of the most terrible in Greek myth. The women of Thrace, devotees of Dionysus, the god of wine and ecstasy, fell upon him in a frenzy and tore him limb from limb, either because he had turned from the worship of Dionysus to the worship of Apollo, or because he had spurned their advances after the loss of Eurydice. His head, still singing, floated down the River Hebrus and across the sea to the island of Lesbos, where it was enshrined in a cave and gave prophecies until the day Apollo silenced it. Calliope, in her grief, recovered her son's head from the waters and had it buried on Lesbos, where the nightingales were said to sing more sweetly than anywhere else in Greece. The poet Aeschylus wrote a lost play, the Bassarides, that told this story, and in it Calliope appeared at the end to mourn her son.

Calliope appears in one of the most vivid scenes of Ovid's Metamorphoses, the great Latin poem of transformation. The daughters of Pierus, a king of Thessaly, challenged the Muses to a singing contest, boasting that their own voices surpassed those of the goddesses. Calliope herself stepped forward to answer the challenge. She sang of the rape of Persephone by Hades, of the transformation of the nymph Cyane into a fountain, and of the boy Triptolemus, whom the goddess Demeter taught the arts of agriculture. The nymphs who judged the contest awarded the victory to the Muses, and in their rage the Pierides mocked the judges. Calliope and her sisters turned the presumptuous girls into magpies, birds that chatter and squawk, condemned to repeat the words of others for ever. It was a fitting punishment for those who had challenged the source of all original song.