While each piece of media takes place in its own universe, they each focus around Black Rock Shooter, a mysterious black haired girl who possesses a burning blue eye and a powerful cannon that can shoot rocks at high speed. Other characters also appear in more than one form of media.

The OVA focuses on a girl named Mato Kuroi, who befriends another girl, Yomi Takanashi, upon entering school. As the two start to drift apart, with Yomi becoming jealous of Mato's friendship with Yuu Kotari, Yomi suddenly disappears. As Mato searches for her, she is taken to a strange world where she meets the mysterious Black Rock Shooter, who merges with her and helps her search for Yomi, fighting off the evil Dead Master who possessed her. The television series uses the same characters from the OVA in a similar but slightly different storyline. As Mato enters middle school and becomes friends with Yomi, she soon faces personal troubles and the influence caused by another world where Black Rock Shooter fights other girls.

The manga series, Black Rock Shooter: Innocent Soul, follows Black Rock Shooter and her serpent partner, Ron, as they venture the Hazama, a world between Heaven and Earth where stagnant souls that have had regrets become trapped. Left alone, these souls can become demons that can pull in other souls, so it is up to Rock to stop them so they may ascend to heaven. Black Rock-chan is a comedy series following the everyday life of a chibi styled Black Rock Shooter named Rock-chan and her babysitter De-chan.

In the video game, which takes place in the year 2051, Black Rock Shooter is awoken from slumber and enters a futuristic battlefield where alien forces have invaded the Earth and have been terrorizing the planet for 19 years. She must fight off the aliens, while also trying to regain her memories.