Jeffrey Magee's parents were in a trolley when a drunk driver crashed and sunk it into the Schuylkill River in Bridgeport, Pennsylvania, orphaning him at age three. After living with his Aunt Dot and Uncle Dan in another town and enduring their mutual hatred and silence for eight years, he runs away during a school musical performance. One year and 200 miles later, he finds himself across the river from Bridgeport in Two Mills, where Hector Street divides the East End from the West End.
He meets Amanda Beale, an East Ender who carries her suitcase full of books to keep them away from her little brother and sister, Hester and Lester, who crayon everything in sight, and borrows one before continuing his dash through town. Along the way, he intercepts a football pass made to local football star James "Hands" Down, infuriates gigantic little leaguer John McNab by hitting home runs off his fastball, and saves an unlucky child from Finsterwald’s backyard, which is full of negative energy. Because of these acts, he earned the nickname "Maniac" and started a local legend.
When "Mars Bar" Thompson corners Jeffrey and rips a page from Amanda's book, he is rescued by Amanda. He finds a home there, helping Mr. and Mrs. Beale with the chores and pacifying Hester and Lester. Soon though, a few East Enders make it clear to him that they don't want him in there anymore by writing racist graffiti on the Beales' front door, "Fishbelly go home" to be exact. His final effort to gain acceptance is by untying the famous Cobble’s Knot. After finishing the task he is praised by everyone as confetti is thrown into the air. Amanda realizes, too late, that it was made from the pages of her favorite book, an encyclopedia A Edition. Jeffrey runs away, taking shelter at the buffalo pen at the zoo.
At the zoo, Jeffrey meets Earl Grayson, a minor-league baseball pitcher who turns out to be a groundskeeper, who never learned to read, and who insists he has no stories to tell. For a few months Jeffrey has a home again with him, helping him at work, celebrating holidays with him, and teaching him to read. Grayson winds up dying 5 days after Christmas, and Jeffery runs off again.
On the verge of death he encounters Piper and Russell, child ruffians that turn out to be John McNab's brothers. He leads them back home, bribing them with free pizza, and stays at their cockroach-infested, waste filled house. Here, he finds the worst that the West End has to offer, as he learns that the McNabs are making a bunker because they believe the East End is planning a rebellion. He endures the coarseness and squalor of their home in hopes of keeping Piper and Russell in school and under control, but he is kicked out when he crushes Piper and Russell's toy guns.
After beating Mars Bar in a foot race and goading him into crashing Piper's birthday party at the McNabs' house, Jeffrey is homeless again. He moves back into the buffalo pen, and runs for miles every morning before Two Mills wakes up. Before long, Mars Bar starts running with him as if by coincidence, and they never say a word to each other. One day they come across a hysterical Piper McNab, who frantically leads them to Russell, stuck on the trolley trestle where Jeffrey's parents died. He walks away silently, nearly unconscious and stunned by fear, while Mars Bar rescues Russell, becoming a hero in his eyes. Jeffrey retreats once again to the buffalo pen, where Mars Bar leads Amanda to it. She brings him to her house in a huff, with Jeffery and Mars Bar following her.