Peter Parker was a student at Midtown High School when he was bitten by the radioactive spider that granted him his powers. Despite being socially incompetent, Peter was an academic success and the top student at Midtown High. His science teacher, Mr. Warren, the brother of Miles Warren, grew quite fond of Peter and became his favorite student. However, Peter was shunned by many of the students and bullied by others. Top on the list of his tormentors was football star, Flash Thompson, who gave him the nickname "Puny Parker". Other students have included Liz Allan, who initially disliked Peter but eventually grew attracted to him, Sally Avril, who would later become known as the adventurer Bluebird, Charlie Weiderman, a student even more bullied than Peter who later in life became encased in living Vibranium, and Jessica Jones, a lonely girl with a crush on Peter who grew up to be a private investigator and married Luke Cage. Villains who have menaced the student body include the Living Brain and multiple Mysterios (Klum and Beck).

Peter returned to Midtown High to become a science teacher, but, in the aftermath from publicly revealing his secret identity, is currently working in disguise as an assistant to Flash Thompson, who now coaches at the school.