Hesiod places Orthrus within the great monster family of Typhon and Echidna. He is the first of their named offspring, followed by Cerberus, the Hydra and the Chimera. The poem gives Orthrus a function immediately: he is the hound of Geryon, the western ruler whose cattle graze in sea-girt Erytheia.

Later writers make Orthrus's appearance more explicit. Pseudo-Apollodorus calls him the two-headed watchdog of Geryon's red cattle. Ancient artists generally follow that identity, although surviving images vary and sometimes add serpent features to his tail. The two heads are the stable feature that distinguishes him from his more famous brother Cerberus.

Orthrus's own descendants are less certain than his parents. Hesiod's wording says that Orthrus mates with a female figure who then bears the Sphinx and the Nemean Lion, but the pronoun is ambiguous. Many modern editors and mythographers take the mother to be the immediately preceding Chimera, while some translations and ancient readers understand Echidna. The safest Mythopouch wording therefore keeps Orthrus as father in the Hesiodic line but marks the mother's identity as uncertain.

During Heracles's tenth labour, the hero crosses Ocean to reach Erytheia and camps on the island. Pseudo-Apollodorus says Orthrus smells the stranger and charges him. Heracles kills the dog with his club, and when the herdsman Eurytion comes to help, he is killed as well. Only after the two guardians fall does Menoetes carry news of the attack to Geryon.

Orthrus receives no resurrection or later quest. His death is the opening violence of the Geryon episode, clearing the way for the fight between Heracles and the three-bodied ruler. Ancient vase painters often place the dead or wounded hound beneath the larger battle, turning the animal into a visual marker that the guarded herd is already being lost.

Orthrus is sometimes overshadowed by Cerberus, but the two hounds serve complementary borders in Greek myth. Cerberus guards the dead below the earth, while Orthrus guards living cattle at the western edge of the world. Both belong to the same monstrous family, but Orthrus's doubled head and pastoral function make him a distinct guardian rather than merely a lesser version of the hound of Hades.