- Maxwell "Max" Kane is the main protagonist and narrator of the story. He is described to be very big and have a striking resemblance to his father, Kenneth "Killer" Kane. In daycare, Max earned the nickname "Kicker" because he had a thing of booting and kicking anyone who dared to touch him, when he was a child. Max lives with his grandparents, Grim and Gram, and usually stays in "the down under", a small room in the basement. He hates his father, whom he witnessed killing his mother, Annie. He becomes best friends with Freak, who customarily rides on his shoulders and acts as Max's surrogate "brain" while Max acts as Freak's legs. Max becomes depressed after Freak dies, locking himself in the down under for days until Grim told him to go back to school. He is also very insecure about himself. He usually calls himself a "butthead", has low self-esteem, and is never confident. Max has dyslexia and is unable to read or write until Freak came along.
- Kevin "Freak" Avery is a disabled, blonde-haired boy whom Max becomes best friends with. Kevin has Morquio syndrome, where the outside of his body cannot grow. He walks on crutches and wears a leg brace. He is a genius for his age and size and is cuttingly sarcastic. He carries a dictionary with him. He is interested in robotics and the tales of King Arthur, to the extent of calling his mother Gwen "The Fair Gwen Of Air/Guinevere" and calling his adventures with Max "quests". Kevin looks forward to his surgery (which Max later finds out was a lie so he wouldn't know the truth), in which he will gain a robot's body. Unexpectedly on his 13th birthday, Kevin has a seizure. In the hospital, he dies, because as his doctor puts it, "his heart became too big for his body." In the film, Kevin's last name was changed from Avery to Dillon.
- Grim is Maxwell's grandfather. His behavior is at first described as quite grim - thus explaining why Maxwell gave him the nickname - though he shows himself to be a kind and friendly person. However, he is extremely hostile towards Max's father due to the murder of his daughter, Annie. In the book, after Grim hears about Killer Kane's parole, he threatens to shoot Killer Kane with a gun if he sets foot in the house. At first, Grim feels sorry for Kevin, but later, he appreciates Kevin's abilities and intelligence.
- Gram is Maxwell's grandmother. Like her husband, she also dislikes Kenneth and misses her daughter, Annie. Gram is quite kind and polite, careful not to hurt anyone's feelings. She protests against shooting Kenneth once Grim announces that he will do so.
- Gwen "Fair Gwen" Avery is Kevin's mother. Kevin nicknames her "Fair Gwen" after King Arthur's beautiful wife, Fair Guinevere. She and Maxwell's mother were friends until Kenneth Kane came along and killed her. After her son's death, Gwen moves to California and starts a relationship with a man named Rick.
- Kenneth "Kenny" David Kane (also known as Killer Kane) is the main antagonist of the book. He is Max's selfish and sociopathic father. He was sent to prison for strangling his wife to death. After his release from prison on parole, Kenny kidnaps Maxwell on Christmas Eve and takes him to Loretta and Iggy's apartment. Loretta Lee tries to save Max but ends up getting strangled by Kenneth, though she survives. Eventually, Kevin rescues Max by spraying a mixture of soap, vinegar and curry powder in Kenny's eyes, which he claimed was sulfuric acid. In the end, Kenny is jailed and has to serve out the rest of his original sentence plus ten years. In the film, he is sentenced to life in prison with no possibility of parole.
- Loretta Lee is a thin, red-haired lady whose stolen purse is recovered by Freak and Max. She is married to the leader of a motorcycle gang named The Panheads, Iggy. Loretta is an alcoholic and a smoker and lives in the "poor" part of the town, the New Tenements. When she attempts to help Max escape, she is almost strangled to death by Kenny Kane, who cracks a bone in her neck, but she turned out okay.
- Iggy Lee is an alcoholic, like Loretta, and lives with her in the Testaments. He is the boss of The Panheads, a motorcycle gang. It is suggested that he may have vertigo, as he states it makes him nervous looking up. He was also a friend of Maxwell's dad (Killer Kane), who makes him scared and nervous. He attempts to help rescue Max when he was kidnapped by his father. He is the husband of Loretta Lee.
- Dr. Spivak is Kevin's doctor. She tells Max about Kevin's death and that the real cause of his death was his heart growing too big for his body.
- Annie Kane is Maxwell's mother but does not appear in the book. She was brutally murdered by her husband, Kenneth Kane.
- Tony D. is a juvenile delinquent who first encountered Max and Freak during the Fourth of July drunkenly asking them for M-80 fireworks. He along with his gang tried to harm Max and Freak with a knife. His gang steals Loretta Lee's purse. He later tells Max he's sorry about Kevin (Freak), who died after having a seizure, though Max doesn't like it and wants to be enemies with him. He is also known as "Blade".
- Rick is a minor character who does not appear in this book. After Kevin Avery dies, he starts a relationship with Gwen Avery in California.
- Mr. Meehan is Maxwell's reading skills tutor.
- Mrs. Donelli is Maxwell's new English teacher.
- Mrs. Addison is the school's principal.
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