Callisto's origins are unknown, although she has claimed that the scars she bears are proof of "how dumb a mistake" it was for her to try to live among normal humans; in one of her earlier appearances, her greatest psychological fear is the image of the beautiful woman that she once was, although she may have overcome that as of the present. When Callisto first appeared she was leader of the Morlocks, a group of mutants who lived in the sewers (named after H.G. Wells's characters in The Time Machine), though she soon lost her role as leader to Storm in a duel. The Morlocks were first formed well over twenty years ago by Callisto, Sunder, Caliban, and Masque.

Callisto kidnapped Archangel and stripped him of most of his clothing, intending to make him her mate. Callisto also attempted to cripple Archangel (then still calling himself Angel) by cutting away his pin feathers. Storm defeated Callisto and stabbed her straight through the heart, nearly killing her, which lead to the X-Men escaping.

Callisto violated Storm's edict that the Morlocks were no longer allowed to kidnap or terrorize surface-dwellers when she arranged Shadowcat's kidnapping. Callisto intended to force Shadowcat (Kitty Pryde) to honor a promise she made to Caliban to stay with him if the Morlocks allowed her teammates to leave the tunnels. Callisto arranged Kitty's kidnapping by having Masque transform the body of a dead homeless girl into Kitty's likeness with his flesh-shaping powers. This body was used as a decoy to convince Storm that Kitty was dead, while the real Kitty was taken underground. Caliban eventually chose to allow Kitty to return home to the school, unwilling to force her to be with him.

Callisto regards Storm with both resentment and respect due to Storm defeating her in hand-to-hand combat, but she sneers at what she considers Storm's "weakness," namely her conviction not to take a life, or to take revenge on baseline humans that despise mutants. The two women fought again while the city of New York was enslaved and ensorcelled by the wizard Kulan Gath. Callisto was previously romantically involved with Colossus (Piotr Rasputin) while he still assumed the identity of the artist Peter Nichols. This followed Peter's journey through the Siege Perilous. The two became attracted to each other after Masque reshaped Callisto's flesh, restoring her beauty to greater than what it was before she was scarred prior to taking refuge in the Morlock tunnels.

After Callisto began a career as a fashion model and moved above ground, the Morlocks attacked her, under the influence of Masque, who sought to wrest leadership of them from her. Masque had grossly transformed the Morlocks, leaving them with grotesque physical mutations. They subsequently renamed themselves Gene Nation and nearly beat Callisto to death. The Morlocks' Healer treated her wounds, but accidentally restored Callisto's scars and her original physical deformities. Callisto retaliated by killing him.

Callisto vowed revenge on her former followers for stealing away her looks, and then allied herself with Mikhail Rasputin, Colossus' older brother. Mikhail and Callisto appeared to have perished when he used his powers over matter to flood the Morlock tunnels. They both later reappeared alive.

More recently, Callisto was transformed by the mutant Masque, having her arms reformed into tentacles. Callisto was also under Masque's control in "The Arena," an elite fight club in Japan. Callisto and Storm battled each other in the Arena, but later both escaped with help from Storm's friend, Yukio.

Last seen, she was one of the main characters in the new Excalibur title, where she was helping Professor Xavier and Magneto rebuild Genosha. Ironically, this alliance briefly (and perhaps uncomfortably) reunited her with Archangel.

Callisto also has a maternal relationship with Marrow, acting as a mother-figure towards the young mutant, (though the two are not biologically related) making her the only person Marrow would follow nearly blindly. However Calisto care for Marrow seems to have droped as that Calisto never mentiod her again anywhere after the six month gap.