Punkzilla begins with Jamie Wyckoff, a fourteen-year-old runaway, riding a Greyhound bus from Portland to Memphis the day after doing meth for the first time. He's on his way to visit his older brother Peter, a.k.a. P, a twenty-seven-year-old gay playwright who also fled their Cincinnati home to get away from their dad, a retired army dude they call the Major.
After Jamie got caught stealing a DVD player from a Service Merchandise store, the Major shipped him off to Buckner, a military school in Missouri. Buckner was as hellish as home, though—maybe even more so—and Jamie was a complete and utter failure as a cadet. Unable to master rifle drills and push-ups, Jamie ran away in the middle of the night and hitchhiked as far as he could go, which turned out to be Portland, Oregon.
Jamie sent P a letter from Washington House, the sketchy transient hotel where he landed. P wrote back to say he was dying of cancer and probably wouldn't make it another three months. He enclosed two hundred bucks and asked Jamie to buy a bus ticket and come to Memphis to say goodbye.
Jamie bought the ticket, but he only makes it as far as Idaho before getting jumped in a bus station men's room. When he comes to and realizes the bus left without him, he starts hitching again, ultimately traveling across the country with a number of shady characters, including an eight-year-old video game junkie, a woman who wants to believe he's her dead son, an obese man who smells like pee, a woman with a leaky eye, and a janitor with a penchant for young boys.
The two bright spots in Jamie's travels are Lewis, a transgender man who loves Salisbury steak and Scarlett Johansson, and Albertina, a teenage girl with lupus to whom he loses his virginity. Ultimately, he does a somewhat sketchy modeling gig and earns enough money to pay for another bus ticket.
When Jamie finally gets to Memphis, he's too late: P's in hospice care and never regains consciousness. Jamie sits on a hill and watches P's funeral from afar, managing to avoid the rest of the family. Jorge takes him in, and he vows to start a new life in Memphis, free of the Major, military school, and (hopefully) meth.