Wesley F. Gibson is a loser cubicle rat who is abused by almost everyone in his life, including his boss, a local gang, his unfaithful girlfriend, and his best friend with whom his girlfriend is having an affair. Wesley was raised by his pacifist mother after they were abandoned by his father, causing him to grow up into a wimp. All this changes when he is visited by the Fox, an assassin who shoots everyone in a sandwich shop before revealing herself to be a member of the Fraternity, a powerful organization of supervillains that rules the world. So long as they maintain secrecy, they are able to commit any crime without any consequences. The Fraternity wishes to recruit Wesley to replace his father, a supervillain known as the Killer, who was killed by an unknown assassin.
The Fox introduces Wesley to Professor Solomon Selzer, a brilliant mad scientist and leader of the North and South American chapter of the Fraternity. The Professor helps Wesley realize his powers by provoking him into shooting the wings off flies. The Professor explains that a long time ago, the world (identified offscreen as a variation of the DC Universe) was overrun by both superheroes and supervillains. Tired of being repeatedly defeated and jailed, the supervillains joined together and staged a revolution that Wesley's father was a part of. After a long, bloody war, the superheroes were defeated. Using magic and advanced technology, the newly formed Fraternity was able to erase the world's memories of superheroes and supervillains. All that remained were faint, inaccurate memories, which were the cause of superhero comic books and other media. Many of the surviving heroes now believed themselves to be actors who had played superheroes.
The Professor also explains to Wesley that Fox and his father had once worked for Mr. Rictus, who controlled the Australian chapter of the Fraternity. When Rictus visits the Professor's headquarters, Fox implies that she and the Killer left Rictus' chapter because he had been harming children.
The Fraternity begins training Wesley to use his newfound powers. The training focuses on not just his physical skills but on his personality. He is desensitized to violence and eventually learns to enjoy it. He is told to commit random acts of violence before undertaking acts of revenge on anyone who even slightly wronged him. He soon becomes a full-fledged Fraternity member, accompanying them on raids of alternate universes and other missions.
Wesley is assigned to be the Professor's personal bodyguard during a Fraternity convention in which the leaders of the Fraternity's five chapters will meet. The five leaders are the Professor, Mr. Rictus, Adam-One, the Future, and the Emperor. Here, he learns that Rictus and the Future had long wanted to end the Fraternity's policy of secrecy and rule the world openly. The Professor, Adam-One, and the Emperor favored secrecy for supervillains in order to get "the loot without the leg-breaking" and avoid gaining the attention of the larger multiverse, and have always managed to outvote Rictus and the Future. Though it seems that the Emperor is about to switch sides, the Professor subtly manipulates him to vote in favor of secrecy yet again.