Set in the rural South in the 1970s in a Catholic school, four pre-teen boys (Kieran Culkin, Emile Hirsch, Jake Richardson, and Tyler Long) create a comic book called "The Atomic Trinity" to channel their creativity, imagination, and rebellious adolescent angst. They each develop their own superhero and, in doing so, live out fantasy lives through their empowered, unchained alter egos. Their evil adversaries are exaggerated characters designed after their teachers: Sister Assumpta (Jodie Foster) the stark, peg-legged nun; and Father Casey (Vincent D'Onofrio), the shady, chain-smoking priest.

The spotlight of the film shines clearly on the handsome Francis (Hirsch) whose crush on his neighbor and schoolmate, Margie Flynn (Jenna Malone), leaves him tongue-tied. Tim (Culkin) is bolder, and so he rewrites a William Blake poem and uses it to bring together secretly dark Margie with wide-eyed Francis. Their relationship flowers into one of the heavier and more mysterious subplots in the film. Margie is instantly written into the comic as a wounded warrior-heroine who enlists the superheroes to help her in her battles against evil. Meanwhile, the boys are busy planning and occasionally executing devilish pranks at school, eventually taking things a step too far, to tragic result.