When Callisto was a young girl, she watched her village burn to the ground and her family murdered in a raid by Xena and her army. Even though Xena did not want to kill the women and children, her general defied her order and the town of Cirra was completely destroyed. The memories of the horror caused Callisto to become bitter and learn the ways of the warrior in order to avenge her loss. This bloodlust caused Callisto to go on a rampage of terror using Xena's name in order to ruin her reputation. After capturing Gabrielle, Callisto faced Xena in battle for the first time, with Xena emerging as the victor. This imprisonment did not last long as Callisto broke free of her dungeon. She proceeded to kill Perdicas, Gabrielle's new husband, which sent Gabrielle into a rage as she coerced Xena into allowing her revenge against Callisto. Another battle was waged where the two warriors ended up in a quicksand pit. Xena escaped the trap, but did not help Callisto to free herself.

Working with Ares, Callisto was free to return to the world in Xena's body. She and Ares worked through Xena's dreams of guilt following the death of Callisto in the quicksand. Xena was given a chance to redeem herself by Hades, but in the body of Callisto. Callisto meanwhile planned to use her identity as Xena to kill Xena's mother and village. Xena was able to catch Callisto and send her into Dreamland. There Xena played the guilt back onto Callisto, sending her back to Tartarus. Callisto manages to escape the Netherworld with the help of Hera, queen of the gods. Although she failed to complete her mission to destroy Hercules, she became an immortal. Hercules trapped Callisto in a dreary, unescapable cave and doomed her to an empty life as an immortal.

Doomed to spend an eternity in the cave, Callisto is freed by Xena, who needed her help to destroy Velasca. Velasca, an amazon warrior who became a God after eating ambrosia, had to be killed by an immortal, so Callisto obliged (against Gabrielle's strong wishes). After fighting with Velasca, the two fell into a lava pit only after Callisto had gained her Godhood as well. Callisto is again freed, but by Hope, the child of Gabrielle and Dahak (the devil). Callisto goes on a rampage with Gabrielle's daughter Hope, killing Xena's son (Solan) and his father Kaleipus. Although Hope was killed by Gabrielle, Callisto was still free as a God.

Callisto is given a chance to re-live her life by traveling through to change the past if she were to kill Hercules before he was born. Callisto succeeds in her task at first, but Iolas steals the chromostone from Xena (from her days as an evil warlord) and goes back to save Hercules' mother. The tables are turned as Callisto free's an adult Hope in order to get oblivion for herself. Callisto makes a deal with Xena that she will kill her with hinds blood. Xena does, and Callisto remains "dead" for a season.

As it turns out, Callisto didn't get the oblivion she desired, instead she was sent to Hell. In Hell, her Master sent her to Rome to lure Xena off her "way" without physically harming her. Callisto failed and Xena was crucified. Callisto was then sent back to Hell. An Angel Xena then traveled to Hell and when she was faced with Callisto's suffering she "lifted" Callisto's damnation and liberated Callisto to an Angel status. Callisto then helped bring Xena and Gabrielle back to life, and her soul was reincarnated as Eve, Xena's child.