The plot of Heroes is designed to be similar to the stories of comic books with small story arcs built into the series' larger story arc plot. Each season of Heroes is designed to involve ordinary people who discover extraordinary super powers, and how these abilities take effect in the character's daily lives.

The first season, known as "Genesis", begins as a seemingly ordinary group of people gradually becomes aware that they have special abilities. Events illustrate their reactions to these powers, and how the discovery affects their personal and professional lives. At the same time, several ordinary individuals are investigating the origins and extent of these abilities. Mohinder continues his late father's research into the biological source of the change, while Noah represents a secret organization known only as "The Company". While coping with these new abilities, each of the characters is drawn, willingly or unwillingly, into the Company's conspiracy to control superpowered people and into a race to stop an explosion from destroying New York City.

Season two, known as "Generations"  begins four months after the events of Kirby Plaza. The main plot arc of Generations deals with the Company and its research on the Shanti virus. This research is explored through the Company's founders, whose identities are revealed, as well as through the effects of various strains of the virus. The heroes ultimately come together in an attempt to stop the release of a deadly strain of the virus and avert a global pandemic.

Claire Bennet
The first part of season three was known as "Villains". Volume three began with the assassination attempt on Nathan, and explores its consequences. In addition, several villains escape from the confines of Level 5, and the Company attempts to recapture them. Arthur Petrelli (Robert Forster) heals from systemic nerve damage and aims to create a formula to give ordinary people abilities. The second part of season three, titled "Fugitives", involves what happens after Nathan fails to produce the formula. After the destruction of Primatech and Pinehearst, the heroes attempt to lead normal lives until Nathan initiates his plan to round up all people with abilities. Sylar kills Nathan in an intense duel; however, Matt is instructed to alter Sylar's mind to believe that he is Nathan.

Season four comprised volume five, "Redemption" and takes place six weeks after the events of season three. The heroes try to return to their normal lives, Peter returns to his job as a paramedic, while Claire attends college. Sylar's acquired abilities begin to manifest as Nathan struggles to maintain his identity and Sylar's consciousness, trapped in Matt Parkman's mind, taunts him and seeks out his body. A carnival group is introduced, led by Samuel, who tries to recruit more people with abilities into his carnival family in hopes of creating a community for these people where they are welcome to be open with their abilities and respected by outsiders. The end of the Season 4 finale begins Volume Six, "Brave New World", in which Claire reveals the existence of people with special abilities to a group of reporters and photographers.