After directing documentaries, he debuted as a feature director with the admired World World War II drama Achtung! Banditi! (1951). Respected for his awarded drama Chronicle of Poor Lovers (1954), he has proven a solid director of genre films, notably crime films such as The Violent Four (1968) and Crazy Joe (1974) or crime-comedy Roma Bene (1971). His film L"oro di Roma (1961) examined events around the final deportation of the Jews of Rome and the Roman roundup, grande razzia, of October 1943.
Lizzani worked frequently for Italian television in the 1980s and supervised the Venice International Film Festival for four editions, from 1979 to 1982.
He committed suicide in Rome at the age of 91, when he jumped from the balcony of his home in Via dei Gracchi on 5 October 2013.