Hughes died of a heart attack during a Thursday morning walk in Manhattan, spokeswoman Michelle Bega said. The 59-year-old was in New York to visit family.
A native of Lansing, Mich., who moved to suburban Chicago and set much of his work there, Hughes rose from comedy writer to ad writer to silver screen champ with his affectionate and idealized portraits of teens, whether the romantic and sexual insecurity of "Sixteen Candles," or the J.D. Salinger-esque rebellion against conformity in "The Breakfast Club."
Hughes' ensemble comedies helped make stars out of Molly Ringwald, Anthony Michael Hall, Ally Sheedy and many other young performers. He also scripted the phenomenally popular "Home Alone," which made little-known Macaulay Culkin a sensation as the 8-year-old accidentally abandoned by his vacationing family, and wrote or directed such hits as "National Lampoon's Vacation," "Pretty in Pink," "Planes, Trains & Automobiles" and "Uncle Buck."
"I was a fan of both his work and a fan of him as a person," Culkin said. "The world has lost not only a quintessential filmmaker whose influence will be felt for generations, but a great and decent man."
Other actors who got early breaks from Hughes included John Cusack ("Sixteen Candles"), Judd Nelson ("The Breakfast Club"), Steve Carell ("Curly Sue") and Lili Taylor ("She's Having a Baby").
Ringwald said in a statement quoted on People.com that she was "stunned and incredibly sad" to hear about Hughes' death.
"He will be missed - by me and by everyone that he has touched," she said. "My heart and all my thoughts are with his family now."
Actor and director Bill Paxton credited Hughes for launching his career by casting him as bullying older brother Chet in the 1985 film "Weird Science."
"He took a tremendous chance on me," Paxton said. "Like Orson Welles, he was a boy wonder, a director's director, a writer's writer, a filmmaker's filmmaker. He was one of the giants."
Hughes films, especially "Home Alone," were among the most popular of their time and the director was openly involved in marketing them. But, with his ever-handy "idea books," Hughes worked as much from personal life as from commercial instinct. His "National Lampoon" scripts were inspired by his own family's vacations. "Sixteen Candles," in which Ringwald plays a teen whose 16th birthday is forgotten, was based on a similar event in a friend's life.
Tall and pale, with a high head of hair and owlish glasses, Hughes caught on just a couple of years after MTV was launched. MTV teens were drawn to his stories and their conflicts about self-discovery and fitting in.
Those who related to his films related in full. They hung posters of "The Breakfast Club" on their walls. They coveted Ringwald's Ralph Lauren boots. They bought the soundtracks, with such MTV favorites as Simple Minds' "Don't You (Forget About Me)." They giggled at and then repeated such naughty dialogue as "I can't believe I gave my panties to a geek" or related to such philosophy as "We're all pretty bizarre. Some of us are just better at hiding it, that's all."
Actor Matthew Broderick worked with Hughes in 1986 when he played the title character in "Ferris Bueller's Day Off."
"I am truly shocked and saddened by the news about my old friend John Hughes. He was a wonderful, very talented guy and my heart goes out to his family," Broderick said.
Hughes was a salesman's son who recalled having a fairly happy childhood, though he was a bit of a loner in high school. An art student at the University of Arizona, he dropped out and returned to the Chicago area, where he began sending jokes - unsolicited - to such comedians as Norm Crosby and Rodney Dangerfield.
He then moved into advertising before becoming a Hollywood screen writer in the late 1970s who, like so many in his profession, tired of seeing his work changed. He wanted to direct. He was unsure how, and afraid to work with experienced actors, so he came up with a simple, youthful plot - a bunch of teens in a single room, which became "The Breakfast Club." (His second release as a director, "Sixteen Candles," came out first.)
Between 1984 and 1990, he wrote or directed more than a dozen hits and acquired enough power to move back to the Chicago area. He remained popular even when his key characters, in "Planes, Trains & Automobiles" and "Uncle Buck," were adults.
But as Hughes advanced into middle age, his commercial touch faded and he increasingly withdrew from public life. His last directing credit was in 1991, for "Curly Sue," and he wrote just a handful of scripts over the past decade. He was rarely interviewed or photographed.
Devin Ratray, best known for playing Culkin's older brother Buzz McCallister in the "Home Alone" films, said he remained close to Hughes over the years.
"He changed my life forever," Ratray said. "Nineteen years later, people from all over the world contact me telling me how much 'Home Alone' meant to them, their families, and their children."