Khan has been one of Egypt's leading cinematic figures since the 1980s, making a string of movies tackling social issues that have often revolved around female central characters.
Khan died in a Cairo hospital early Tuesday following "health problems", state-owned al-Ahram newspaper said. His family was not immediately available for comment.
A British national born to an Egyptian-Italian mother and a Pakistani father in Cairo in 1942, Khan studied in Britain and worked as an assistant director in Lebanon before returning to settle in Egypt.
He directed 24 feature films starring the country's leading actors and actresses, denouncing the oppression of Egyptian women and fighting social ills in films that were acclaimed by critics and the public alike.
In his 1987 film "The Wife of an Important Man", Khan portrayed a police officer who is intoxicated by power and involved in the repression of opponents of the regime.
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The film in 2013 made it onto the Dubai International Film Festival's top 100 Arab films of all time.
The same year, Khan's film "Factory Girl" won two prizes at the same festival, including a prestigious critics award.
The film tells the story of Hiyam, a young factory worker living in a lower-middle-class neighbourhood of Cairo, who falls in love with her supervisor.
Khan leaves behind his wife Wessam Souleiman, who wrote the screenplay for several of his films including "Factory Girl".
His daughter Nadine Khan is also a film director and her feature debut "Chaos, Disorder" won the Special Jury Prize at the Dubai International Film Festival in 2012.
Despite being widely celebrated as a great figure in Egyptian and Arab cinema, Egypt only granted Khan nationality in 2014.
Egyptian women married to foreigners were not allowed to pass on their citizenship to their children prior to a 2004 amendment to the nationality law.