Hughes was working with the Nation Lampoon magazine when he decided to pen a story, Vacation 58, based on the family trips he had taken as a child. He had earlier tried his hand at writing comedy, first by penning jokes for performers like Joan Rivers and Rodney Dangerfield and then by writing the screenplay for Class Reunion. It was Vacation 58, that earned him success. Vacation 58 was made into National Lampoon's Vacation film, which built Hughes's career as a writer, director and a producer. Hughes went on to turn out teen comedies that captured the spirit of the eighties – whether it was his directorial debut with Sixteen Candles, The Breakfast Club, Ferris Bueller's Day Off, Pretty in Pink or Weird Science.

Hughes did not confine himself to teen movies and he went on to make Planes, Trains and Automobiles (starring Steve Martin and John Candy), Uncle Buck and Career Oppurtunities. He also wrote the semi-autobiographical She's having a Baby as well and more recently Maid in Manhattan. Hughes also concentrated on comedies based on children - from the ever popular Home Alone 1 and Home Alone 2 (Lost in New York) to Dennis the Menace, Beethoven, Curly Sue, Miracle on 34th Street, Baby's Day Out and 101 Dalmations – all of which (with the exception of Beethoven) were written and produced by him.

Curly Sue was the last film he directed after which he moved on to Wisconsin and took to farming. Though he still wrote and produced films including The Miracle on 34th Street, Home Alone 3 and the the Robin Williams-starrer Flubber, he rarely made public appearances or gave interviews. On August 6 2009, he collapsed and died after a heart attack while on a family visit to Manhattan. He is survived by his wife Nancy, two sons and four grandchildren.