In the mirror universe, Talos IV was the homeworld of the Talosian species.

Just as in the Federation universe, this Talos IV had been rendered almost completely uninhabitable due to centuries of warfare. Moreover, in the early 23rd century an Earth ship had crashed on its surface with only one survivor, Vina. Again, just as in the Federation universe, the Talosians had used a distress call to lure the Enterprise to the planet with the intention of having Captain Christopher Pike mate with Vina so as to create a race of Human slaves.

However, upon learning of the Terran Empire's fear of telepaths, the Talosians decided to release Captain Pike and use him as their eyes and ears throughout the empire. The Captain would give the Talosians an early warning should the empire ever decide to attack and obliterate their planet.

Although classified by Starfleet, Lieutenant Commander James T. Kirk was able to learn the details about what had occurred on Talos IV through Spock. After he assassinated Pike, Kirk assumed the captaincy of the Enterprise and ordered the ship to Talos IV while he attempted to shield his mind from the Talosians by focusing on thoughts of intense rage. Upon arriving at the planet, Kirk ordered its surface to be leveled, annihilating the entire race of telepaths for the good of the empire. (TOS short story: "The Greater Good")