As the title implies, Maniac, whose real name is Jeffrey Lionel, is the most important character in the novel. All others revolve around him. Maniac is almost a modern version of Huck Finn. His parents died in a trolley accident when he was three years old, and he lives for several years with an eccentric Aunt Dot and Uncle Dan who are married only in a legal sense and really hate each other. When Maniac shouts out to them, above the voices of his classmates as they perform a school play, "Talk! Talk, will ya!" he is so upset that he begins to run, and Spinelli says, a legend is born. Readers hear no more until this strange boy shows up a year later in Two Mills, two hundred miles from Hollidaysbury.

The characters who influence Maniac are mostly from this new hometown. First, he meets Amanda Beale and her family, who are friendly, warm, compassionate, and black. They realize this scraggly white kid is homeless and invite him to live with them. All is well, until neighbors scrawl "Fishbelly Go Home" on the Beales's house. Even though he unties Cobble's knot, opposing gangs make him realize that his presence is causing the family trouble, and he leaves.

Maniac lives among the buffaloes at the zoo until he collapses and is found by an illiterate caretaker named Grayson who feeds and cares for him. In addition to being humorous and caring, Grayson, a former minor league baseball player, is totally naive about how "black people" live. He is amazed that they eat meatloaf and use toothbrushes. "Ain't that somethin'," he says to Maniac. In addition to being open to the strange habits and tales of this unusual boy, Grayson proves to be a fast learner when Maniac teaches him to read. They enjoy a meaningful holiday season, during which they have "cookies and carols and colored lights and love" before Grayson dies, five days after Christmas.

Naturally, Maniac is very affected by the death of this surrogate father. He vows that he will not be orphaned again, and he spends his days running or doing odd jobs, while he sleeps wherever he can at night—junk cars, basement stairwells, empty garages. Finally, he finds that he has run to Valley Forge and patiently awaits his death.

Maniac's wait is interrupted when he encounters two young runaways, Piper and Russell McNab. He convinces them to let him take them home. He lives with them a short time, and he finds that their white family is the exact opposite of the Beales. They are loud and obnoxious, and they live in a filthy, rat-infested house frequented by their older brother's gang, the Cobras. They see blacks as "today's Indians" and spend their time building a fortress to protect themselves against the time when racial conflicts will break out.

In an effort to bring the East Enders and West Enders together, Maniac takes Mars Bar Thompson to the West End. Spinelli describes this young man as follows: "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." First, they visit the Pickerell family where cultural differences are no problem, and the visit is successful. The opposite occurs at the McNab birthday party, where Mars Bar is practically attacked and has to be restrained from retaliating. After this behavior, the younger McNabs later rely on Mars Bar to rescue them from the trolley trestle and go home with him where his mother pampers them all...