He had been in a coma in hospital for two months after being admitted with respiratory problems.
Trained as a carpet designer, Ghitani took up journalism in his 20s and went on to write historical fiction.
Much of his work has been widely translated, including the 1974 novel Zayni Barakat, considered a seminal portrayal of authoritarian rule.
Set in the Mamluke era, the novel was seen as a veiled critique of the regime of President Gamal Abdel Nasser.
As a journalist Ghitani also reported from the frontlines during the Arab-Israeli conflict of 1973.
He won awards in Egypt for his writing, as well as being awarded France's Chevalier de l'Ordre des Arts et des Lettres in 1987.
Prime Minister Sharif Ismail said that Ghitani had "contributed significantly in enriching literature with his unique style, intelligence and broad vision".
Ghitani was one of several intellectuals who supported the army's ousting of Islamist President Mohammed Morsi in 2013, despite the harsh crackdown against the army's opponents that followed.
Acclaimed Egyptian novelist and journalist Gamal al-Ghitani has died in Cairo, aged 70.