- Jeffrey Lionel "Maniac" Magee is an orphan and finds himself in Two Mills, where he becomes a local legend while trying to find a home. He has astonishing athletic abilities, runs everywhere he goes, can untie any knot, is allergic to pizza, and crosses the barrier between the East End and West End as if blind to racial distinction. He has done many heroic feats such as running for a long period of time, hitting many home runs in a row, entering Finsterwald's backyard, and untying Cobble's Knot. He lived in many temporary homes, even once in a buffalo pen.
- Amanda Beale is the first person Jeffrey meets in Two Mills. She carries her books in a suitcase so they aren't ruined by her younger siblings, Hester and Lester. She defends Jeffrey from Mars Bar and eventually provides him with a home. She is very stubborn. When someone destroys one of her books, Encyclopedia A, she becomes very upset.
- Mars Bar Thompson is the worst kid in the East End. He dislikes Jeffrey's presence in the East End, which is exacerbated when Jeffrey beats him in a race. However, he eventually rescues Russell McNab from the trolley truss, and offers Jeffrey a place for a while. As his nickname implies, he is known for eating Mars Bars. His real first name is never revealed.
- John McNab is infuriated when he cannot strike out Jeffrey with his ball. After acting as a bully, he welcomes him into his home when he brings back John's younger brothers, Piper and Russell, after their attempt to run away to Mexico. He remains convinced that the black East Enders are planning a rebellion.
- Piper and Russell McNab are John McNab's younger brothers who frequently commit truancy, steal, and constantly try to run away from home. In their house, they use toy machine guns to shoot the "rebels" from the East End. Piper also had a party at the end of the book. They made Mars Bar mad at Jeffrey. Later they play on the trolley tracks and Mars Bar saves Russell. They are eight years old.
- Earl Grayson is the groundskeeper at the zoo and resident of the YMCA, though he was once a minor league baseball pitcher who struck out Willie Mays. He becomes friends with Jeffrey, who listens to his stories and Jeffrey teaches him to read. They end up living together in a house, which makes him responsible. He is very kind and cares about Jeffrey. Tragically, Grayson, as he is called in the book, passes away shortly after Christmas, leaving Jeffrey all alone once again.
- Mrs. Beale is the kind and caring mother of Amanda, Hester, and Lester. She is very thoughtful of Jeffrey as well.
- Hester and Lester are the younger siblings of Amanda Beale, and the son and daughter of Mrs. Beale. They are very hyperactive, and will vandalize anything that they can get their hands on.
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