Hughes was born on February 18, 1950, in Lansing, Michigan, to Marion Crawford, who volunteered in charity work, and John Wilden Hughes, who worked in sales. He was the only boy, and had three sisters. He spent the first twelve years of his life in Grosse Pointe, Michigan, where he was a fan of Detroit Red Wings right winger Gordie Howe. One of Howe's #9 jerseys, sent by Howe himself, was later prominently featured in Hughes's 1986 film Ferris Bueller's Day Off. Hughes described himself as "kind of quiet":
In 1963, Hughes's family moved to Northbrook, Illinois, a suburb of Chicago. There, his father found work selling roofing materials. Hughes attended Grove Middle School, later going on to Glenbrook North High School, which gave him inspiration for the films that eventually made his reputation. He met Nancy Ludwig, a cheerleader and his future wife, in high school. As a teenager, Hughes turned to movies as an escape. According to childhood friend Jackson Peterson, "His mom and dad criticized him a lot (...) She [Marion] would be critical of what John would want to do". Hughes was a fan of the Beatles, and allegedly knew a lot about movies and the Rat Pack.