Skullgirls takes place in the fictional Canopy Kingdom. In a world rife with conflict and dirty dealings, several individual and organizations seek to obtain the mysterious artifact know as the Skull Heart. Once every seven years, the Skull Heart grants one young woman´s wish. However, if a woman with a inpure soul attempts to use the Heart, her wish will be corrupted and she will be transformed into the next Skullgirl, a monstrous entity with immense power. Hundreds have sought after the Skull Heart, yet none of its wielders have been deemed worthy and spared of its cruel power.
Seven years following the Grand War, a blood-soaked battle fought between three nations, the newest Skullgirl, has emerged and begun to terrorize the Canopy Kingdom.
The game follows several fighters and their journeys to confront the Skullgirl and claim the Skull Heart. Each character has their own motive for seeking the Heart, whether to destroy the artifact or use its power for their own interests.
Painwheel, a normal schoolgirl who was kidnapped and infused with parasites and experimental Skullgirl blood, turning her into a monster.