As the title suggests, Maniac, whose real name is Jeffrey Lionel, is the central character in the novel. All other characters are connected to him. Maniac is somewhat like a modern-day Huck Finn. His parents died in a trolley accident when he was three years old, and he spent several years living with his quirky Aunt Dot and Uncle Dan. Although married, they despise each other. When Maniac shouts, "Talk! Talk, will ya!" above his classmates' voices during a school play, he becomes so distressed that he starts to run, and according to Spinelli, a legend is born. Readers hear nothing more about him until he reappears a year later in Two Mills, two hundred miles from Hollidaysbury.

The characters who impact Maniac are primarily from this new town. First, he meets Amanda Beale and her family, who are kind, warm-hearted, compassionate, and black. They realize this scruffy white kid is homeless and invite him to stay with them. Everything goes well until neighbors deface the Beales's house with "Fishbelly Go Home." Despite untying Cobble's knot, rival gangs make him understand that his presence is causing the Beales trouble, so he leaves.

Maniac then lives among the buffaloes at the zoo until he collapses and is discovered by Grayson, an illiterate caretaker who feeds and looks after him. Grayson, a former minor league baseball player, is humorous, caring, and completely ignorant about how "black people" live. He is astonished to learn they eat meatloaf and use toothbrushes. "Ain't that somethin'," he remarks to Maniac. Grayson is also open to the peculiar habits and stories of this unusual boy and proves to be a quick learner when Maniac teaches him to read. They share a meaningful holiday season filled with "cookies and carols and colored lights and love" before Grayson passes away, five days after Christmas.

Understandably, Maniac is deeply affected by the death of this surrogate father. He vows never to be orphaned again and spends his days running or doing odd jobs while sleeping wherever he can at night—junk cars, basement stairwells, empty garages. Eventually, he finds himself at Valley Forge, where he patiently waits for death.

Maniac's wait is interrupted when he meets two young runaways, Piper and Russell McNab. He persuades them to let him take them home. He stays with them briefly and finds their white family to be the complete opposite of the Beales. They are loud, obnoxious, and live in a filthy, rat-infested house visited by their older brother's gang, the Cobras. They view blacks as "today's Indians" and spend their time constructing a fortress to protect themselves against potential racial conflicts.

To bridge the gap between the East Enders and West Enders, Maniac takes Mars Bar Thompson to the West End. Spinelli portrays Mars Bar Thompson with the description: "If black meant bad, if black meant in-your-face nastiness, if black meant as far from white as you could get, then Mars Bar Thompson was the blackest of the black." Their first stop is the Pickerell family, where cultural differences pose no issue, making the visit a success. In stark contrast, the McNab birthday party turns hostile, with Mars Bar nearly being attacked and needing restraint to prevent retaliation. Despite this, the younger McNabs later depend on Mars Bar to save them from the trolley trestle and accompany him home, where his mother takes care of them all day.

These groups of characters—the Beales, Grayson, Mars Bar, and the McNabs—highlight the book's three central themes. The Beales offer Maniac a home when he has nowhere else to go. Initially, he declines their offer but eventually realizes he belongs with them. Grayson, who is illiterate, learns to read thanks to Maniac. The McNabs and Mars Bar symbolize the bigotry in the world, where people are unwilling to understand each other's lives and cultures. Through Maniac's interactions, he draws out love and goodness from all these characters, ultimately helping them see that black and white people share more similarities than differences.