Vizzini grew up primarily in the Park Slope neighborhood of Brooklyn in New York City. He attended Stuyvesant High School in Manhattan, graduating in 1999. While still a teenager, he began to write articles for the New York Press, an alternative newspaper.

After he wrote an essay that got published by the New York Times Magazine, several of his essays about his young adult life ended up being combined into his first book, Teen Angst? Naaah.... Vizzini attended Hunter College, also located in Manhattan. Ned Vizzini lived in New York City. Vizzini's characters and situations are said be based upon his time spent at Stuyvesant.