The main cast, not all of whom have been shown to possess powers, consists of:

• Noah Bennet (Jack Coleman), more commonly referred to as "Mr. Bennet" or "the Man in Horn-Rimmed Glasses", who works for the Primatech Paper Company, which is actually a cover operation for an organization that investigates people with superhuman abilities.
• Claire Bennet (Hayden Panettiere), Mr. Bennet's adopted daughter, a high school cheerleader who lives in Odessa, Texas, and has a spontaneous regenerative ability.
• Simone Deveaux (Tawny Cypress), an art dealer and gallery owner whose skepticism and complicated romantic life are tested.
• D.L. Hawkins (Leonard Roberts), the husband of Niki and father of Micah, has the power to alter his physical tangibility and phase through solid objects.
• Isaac Mendez (Santiago Cabrera), an artist living in New York who can paint future events during precognitive trances. He also writes and draws a comic book called 9th Wonders! which has also been shown to depict the future. He has problems with drugs.
• Hiro Nakamura (Masi Oka), a programmer from Tokyo with the ability to manipulate the space-time continuum. He is convinced that he is a hero, and with other "special persons", he can change the future.
• Matt Parkman (Greg Grunberg), a Los Angeles police officer with the ability to hear other people's thoughts.
• Nathan Petrelli (Adrian Pasdar), a New York Congressional candidate with the ability of self-propelled flight.
• Peter Petrelli (Milo Ventimiglia), a former hospice nurse and Nathan's younger brother. He is an empath with the ability to absorb the powers of others he has been near and recall them.
• Micah Sanders (Noah Gray-Cabey), D.L. and Niki's son and a child prodigy, Micah is a technopath, allowing him to "talk" to electrical devices, which gives him control of machines and electronic devices.
• Niki Sanders (Ali Larter), the wife of D.L. and mother of Micah. A former internet stripper from Las Vegas who exhibits superhuman strength and an alternate personality who goes by the name of Jessica.
• Mohinder Suresh (Sendhil Ramamurthy), a professor of genetics from India who travels to New York to investigate the death of his father, Chandra. Through his investigations, he comes into contact with people his father listed as possessing superhuman abilities.

The main antagonist in season one is Sylar (Zachary Quinto), a serial killer who hunts super-powered individuals in order to take their abilities. Additionally, the first season slowly reveals who and what is responsible for a plot to destroy New York City. The series also features many guest and recurring characters, including friends and family of the main cast, criminals and villains, and other individuals with remarkable powers.