Jeffrey Lionel Magee is living a normal life until his parents are killed in a tragic trolley accident when he's three. He's sent to live with his Aunt Dot and Uncle Dan, and, despite Dot's sporty name, it's not a fun household. Uncle Dan and Aunt Dot are strict Catholics who hate each other, meaning Maniac grows up in a loveless, largely silent house. When he's 11-years-old, he's finally had enough, and takes off running. Yup, literally running. He runs for a couple hundred miles and a year, and ends up in Two Mills, Pennsylvania.
Maniac doesn't know it yet, but Two Mills is a divided town. (Okay, well, maybe the name should have been a clue.) The East and West End are separated by Hector Street. Maniac's first stop is the East End, where he meets Amanda Beale and her suitcase of books. Maniac goes back and forth between the East and West End, making a few friends, but mostly enemies, and for some reason never really noticing that the West End is entirely white and the East End is entirely black.
When the Beales realizes that Maniac is homeless, they take him in as a member of their family. Life is great for a while, but eventually the East Enders start getting him down. See, not everyone loves the idea of a white kid living with a black family in a black neighborhood. So Maniac (after a quick detour solving Cobble's Knot) takes off.
Long story short, he moves in with a buffalo family and then meets Earl Grayson, a washed-up former minor leaguer. Things are really hunky dory for a while: Maniac's got a dad, Grayson learns to read, they celebrate Thanksgiving and Christmas. And then Grayson dies. And Maniac is alone. Again.
Maniac's not doing so well this time, and ends up cold, starving, and alone in Valley Forge. Good thing Russell and Piper McNab find him on their way to Mexico. These two little hoodlums provide a reason for Maniac to stick around for a while, in a nasty nasty house filled with some nasty nasty people.
But the little McNabs need Maniac, and he steps up. Eventually, Maniac leaves them behind as well to move back in with Baby Buffalo and his mom. (Really.) He's living there when his frenemy Mars Bar Thompson and his adopted sister/BFF Amanda Beale find him and make him come home. That's right, home. To his family. It looks like Maniac has finally found what he's looking for.