The Skullgirl is a powerful female being that is the result of an "impure" woman making a wish using the Skull Heart, an object which later merges with the user. Skullgirls are intended to be mindless servants of the Trinity and are tasked with destroying the world, but those with a strong will such as Marie can resist the Skull Heart's influence. Even those who can resist the Skull Heart however experience considerable changes in their personality, becoming more cold and ruthless over time. Though a sense of mortality can remain, this ability will dwindle as the Skull Heart slowly takes over the holder's body.
Parasites also become corrupted if their host becomes a Skullgirl. They lose their sense of individuality, though whether or not this means they remain as a separate entity or become one with the Skullgirl or Skull Heart remains unknown.
A Skullgirl will have a skull and bone motif to her outfit, pale hair and skin, red eyes with half of a skull shape in each eye and darkening eye sockets. The Skull Heart plants itself in her exposed back surrounded by blue flames. Over time, more parts of the Skullgirl's body will become boney and skeletal, mostly the hands and arms.
Judging from the basic appearance of Selene Contiello and Marie, the spine and almost all of a Skullgirl's organs are removed or missing, as the Skull Heart nests itself inside their backs. Parts of Marie's ribcage is exposed with no visible internals at all.
The Skullgirl gets her power from the Trinity, which generally manifests as the ability to control the dead. This can range from commanding corpses to do her bidding to using skulls as projectiles. However, it is possible to disrupt or block the Skullgirl's influence, such as in the case of Squigly.
Marie also demonstrates command over a giant, shadowy, masculine figure that is always behind her (in her 2nd and 3rd forms) to physically assault her foes.
These characters are shown or implied to become Skullgirls by the end of their Story Mode.
- The giant, masculine figure Marie controls may be the figure of The Great Mother herself.
- The process of transforming into a Skullgirl is painful, as shown in Filia's ending.
- Skullgirls are literally (and strictly) females. In the official Skullgirls Facebook page, it was said as an answer to a comment that only a woman can use the Skull Heart.