"A Certain Scientific Accelerator" is a spin-off of the "A Certain Magical Index" series, centering on Accelerator, one of the most powerful espers in Academy City. The story begins shortly after the events of the "Sisters Arc," where Accelerator, once a ruthless antagonist, begins to grapple with his moral choices and seeks redemption. His path intersects with Estelle Rosenthal, a young girl targeted by a mysterious organization called Disciplinary Action. Estelle carries a dangerous secret: she is a vessel for a necromantic experiment involving the "Clonoth," a tree-like structure that connects the living and the dead.

As Accelerator protects Estelle, he becomes entangled in a conflict involving necromancers, rogue scientists, and other espers. The narrative explores themes of redemption, the consequences of scientific experimentation, and the blurred lines between life and death. Accelerator's abilities, which allow him to manipulate vectors, are central to the action, often pitting him against formidable opponents. The story also introduces new characters, such as the necromancer Kihara Amata and the enigmatic Yomikawa Aiho, who play significant roles in the unfolding events.

The plot delves into the darker aspects of Academy City's scientific endeavors, particularly the unethical experiments conducted in pursuit of power and knowledge. Accelerator's journey is marked by his struggle to reconcile his past actions with his desire to protect those he now cares about. The series maintains a balance between intense action sequences and moments of introspection, highlighting Accelerator's growth as a character. The narrative builds on the established lore of the "A Certain Magical Index" universe while expanding on Accelerator's personal story and the broader implications of the Clonoth experiment.