The filmmaker died on Wednesday at his home in Manhattan, as a result of complications from esophageal cancer. He was surrounded by family at the time of his death, reported Entertainment Weekly.
The director disclosed that he had cancer in 2015.
Demme's most iconic film was "The Silence of the Lambs," the 1991 horror-thriller that was a blockbuster, a critical success, and introduced moviegoers to Anthony Hopkins' Hannibal Lecter.
The story of a novice FBI analyst (Jodie Foster) on the trail of a murderer became only the third film in history to win Academy Awards in all the top five categories, joining the ranks of "It Happened One Night" and "One Flew Over the Cuckoo's Nest."
The filmmaker garnered acclaim for his 1980 comedy-drama "Melvin and Howard". Over the next decade, Demme became one of the most admired directors in the country with films like the black comedies "Something Wild" and "Married to the Mob".
Demme's subsequent films included "Philadelphia," for which Tom Hanks won the best actor Oscar as a lawyer with AIDS, and "Rachel Getting Married".
The Timberlake concert film, "Justin Timberlake + the Tennessee Kids," is Demme's last theatrical directorial credit. He also directed an episode of the Fox series "Shots Fired," which airs Wednesday on the network.
Demme, who was previously married to director-producer Evelyn Purcell, is survived by second wife Joanne Howard and their three children: Ramona, Brooklyn and Jos.
In lieu of flowers, Demme's family asked that donations be made to Americans For Immigrant Justice in Miami.
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