Manfredi studied law and afterwards acquired a diploma from the Accademia d' Arte Drammatica in Rome. He worked in radio and received a first engagement at the Piccolo Teatro in Milan, where he was successful in Molnar's Liliom. He was married to the former photo model Erminia Ferrari. His daughter Roberta and his son Luca are also active in the film business.
In 1948 he made his film debut in the short film Tenori by forza and entered the 1950s in small roles. His first major starring role he played in 1959 in Puccini's Gianni L' impiegato. Early 1960s, Nino Manfredi established himself as an actor with the role of the ill-fated man in Luigi Comencinis Raped in chains (1961 ) and Luigi Zampas Anni ruggenti (1962 ) as a small employee who is mistaken for a powerful fascists. He was involved until the end of the 1970s in numerous Italian - French co - productions, often appeared on TV shows and became a popular comedian of Italian cinema. His grotesque movie characters, including a church dignitary in Luigi Magni In nome del Papa Re (1977 ), the busybody Trafficone in Sergio Corbuccis La mazzetta (1978 ) and the illegal Coffee representative in Nanni Loy's Café Express (1980 ) won him a wide audience. In the 1980s he reduced his work in film and television in favor of more frequent stage appearances.
Manfredi's first film directorial effort was one of the four episodes of L' amore difficile (1962 ), but he was only in 1971 his solo directorial debut with Per grazia ricevuta. For this film, Nino Manfredi 1971 award at the Cannes Film Festival with the award for best first film. His next in 1981 in collaboration with Alberto Lattuada incurred Nudo di donna film had only modest success.
Manfredi was the editor of a collection of Roman phrases and a cookbook.