Callisto's family were killed by Xena's army at Cirra. She has dedicated her life to matching her own skills to Xena's so she can take her revenge on the warrior princess. Callisto is ruthless and psychotic and does not care whom she destroys. Her hatred for Xena is all-consuming and she vows to destroy everything she loves. She partly manages to do this when she murders Perdicas, Gabrielle's childhood friend and husband (see "The Return Of Callisto"). In return, Xena goes after Callisto and they end up having a chariot race across the sands. Both Callisto and Xena fall into some quicksand. Xena manages to escape and is about to help Callisto when she changes her mind and lets her sink into the quicksand instead.

Callisto is given another chance at life by Hera. She manages to trick Hercules into helping her retrieve a golden apple which makes her immortal (see the Hercules episode "Surprise") and, later, she acquires ambrosia and becomes a goddess in "A Necessary Evil". Xena successfully traps her in a lava flow but she escapes from this, with the help of the demonic Hope. She then teams up with Hope, helping her to murder Solan, Xena's son (see "Maternal Instincts"). A grieving Xena manages to trap Callisto in some caves but she later escapes (see "Sacrifice I").

Even after Xena ends Callisto's life by stabbing her with the dagger of Helios ("see Sacrifice II) Callisto manages to return to torment Xena. When Xena refuses Callisto's offer in "Ides Of March", Callisto breaks Xena's back with her chakram to stop her from escaping crucifixion. Not content with dooming Gabrielle and Xena to die, demon Callisto steals Gabrielle's soul from Heaven and descends into Hell, taking Gabrielle with her (see "Fallen Angel"). She then tempts Gabrielle to eat so that Gabrielle will become a demon too. It is only after Xena gives up her place in Heaven by taking pity on Callisto that Callisto loses all her hatred of Xena and becomes as innocent as she was wicked. Now an angel, Callisto chooses to be reborn as Xena's child.