The 95-year-old moviemaker allegedly committed suicide at the San Giovanni hospital in Rome, where he was being treated for a prostate tumour, according to the ANSA news agency.
Monicelli's career began in the 1930s, when he produced numerous screenplays and worked as an assistant director.
He made his directorial debut in 1949 with Toto Cerca Casa and went on to become a critically acclaimed moviemaker, most notably for 1959's La Grande Guerra, which landed him the Leone d'Oro honour at the Venice Film Festival, and an Academy Award nomination for the Best Foreign Film.
Monicelli picked up a string of other awards throughout his career; he was handed the Silver Bear for Best Director at the Berlin International Film Festival in Germany on three separate occasions and was honoured with the Golden Lion trophy for his career at the 1991 Venice Film Festival in Italy.
In recent years Monicelli scaled back his workload, but at the age of 91 he directed 2006's The Roses of the Desert.
After learning of his death, Rome's former Mayor Walter Veltroni paid tribute to the director, saying, "We feel profoundly and humanly hurt by his death, which we know is a loss that weighs and will continue to weigh heavily on us."