Mayberry attended Northwestern High School, graduating in 1967. He was a gifted high school athlete, playing baseball, football, and basketball at Northwestern; John was twice named to the Detroit News All-State Basketball Team. After graduation, Mayberry was selected by the Houston Astros in the first round (sixth overall) of the 1967 Major League Baseball Draft. He was the second first baseman taken in the draft, Ron Blomberg having been selected number one overall by the New York Yankees.