There are several variations on the story of Io in Classical literature. One of the most famous of these versions appears in the Metamorphoses of Ovid.

According to Ovid, Zeus was smitten with Io, so the ruler of the gods devised a way to consummate his relationship with the virgin princess. He caused a cloud to form on a sunny day, and used this cloud to conceal his lovemaking. However, Zeus's vigilant wife Hera noticed the strange dark cloud marring the landscape from her home on Olympus, and immediately her suspicions were aroused. She darted down to earth to investigate. Zeus, in the meantime, had transformed his newest beloved into a stunning white heifer in order to protect his mistress from Hera's notorious wrath.

Upon arriving at the scene, Hera asked about the lovely heifer. Zeus was forced to give Io (in her bovine form) to his wife. But Hera was still not satisfied that Zeus would behave himself. The goddess therefore told Argus (who was a monster with many eyes) to guard the heifer. Zeus did not like this arrangement at all, so he sent his cunning son Hermes to dispatch Argus. After Hermes conquered the guardian monster, Hera became even more angry, and summoned a Fury in the form of a gadfly to sting and pursue the heifer Io relentlessly.

Io wandered far from her home, trying to escape from the gadfly. Finally, she reached Egypt, and in this country she was at last restored to her original form. As a beautiful young woman once again, Io gave birth to a son named Epaphus, her child by Zeus. She was worshipped in Egypt, and identified with the Egyptian goddess Isis.