The director died after a heart attack in New York, his spokeswoman said.
Hughes was the director of such successful films as Ferris Bueller's Day Off, The Breakfast Club, and Planes, Trains and Automobiles.
He was also a leading script writer, penning films such as Pretty in Pink and Home Alone.
Over the past decade, Hughes withdrew from Hollywood and became a famer in the Midwestern state of Illinois.
Hughes had been in Manhattan on a family visit when he died.
1980s zeitgeist
The BBC's Vincent Dowd says Hughes had not directed a film since Curly Sue in 1991, but it did not matter - his early movies had become part of the 1980s zeitgeist.
John Hughes in 1984, the year he directed Sixteen Candles |
If, in 1986, Ferris Bueller's Day Off owed something to the on-screen energy of the young Matthew Broderick, it also benefited from Hughes' sharp script and direction, our correspondent says.
He worked well with young talent, as he had already shown the year before in The Breakfast Club starring Emilio Estevez and Mollie Ringwald, he adds.
In the high-school story, our correspondent says, Hughes cleverly portrayed teen America to itself - and the box office was enormous.
"Many filmmakers portray teenagers as immoral and ignorant, with pursuits that are pretty base," Hughes told the Chicago Tribune newspaper in 1985.
"They seem to think that teenagers aren't very bright. But I haven't found that to be the case. I listen to kids. I respect them. I don't discount anything they have to say just because they're only 16 years old," he added.
'Quintessential filmmaker'
Born in 1950 in Michigan, where he set many of his films, Mr Hughes started out as a journalist and advertising copywriter before trying out script writing.
I am truly shocked and saddened by the news about my old friend Matthew Broderick |
His biggest hit of all came in 1990 with Home Alone, which he wrote and produced, but did not direct.
The film made the central character, a then 10-year-old Macaulay Culkin, the biggest child star for decades and grossed almost $500m (£300m) worldwide.
"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."
In a statement, Matthew Broderick said: "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."
By the mid-1990s, Mr Hughes had disappeared from the public eye almost totally, though he continued to produce and write screenplays.
He wrote under the pseudonym of Edmond Dantes, a character in the Alexandre Dumas novel, The Count of Monte Cristo.
His credits under the name include Beethoven and Maid in Manhattan.
Our correspondent says Mr Hughes will above all be remembered for a small number of movies which perfectly captured the spirit of 1980s America.
Source: bbc.co.uk
I have always been a fan of this man's work. His collaborations with John Candy remain among the most memorable to me.
Films like Uncle Buck, Planes Trains & Automobiles, Home Alone, Ferris Bueller's Day Off and the iconic The Breakfast Club are absolute classics.
The world of entertainment has lost another wonderfully creative soul. He will undoubtedly be sorely missed, but his work will live on and be remembered for future generations to come.
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