Born in Rome, Genina was a drama critic and wrote comedies for the Il Mondo Magazine, under the advice of Aldo de Benedetti switches to movies for the "Film d'Arte Italiana", which produces his first film "La moglie di sua eccellenza". In 1929 Genina moved to France to direct Louise Brooks in the sonorized film Miss Europe. He studied sound techniques and worked in France and Germany in the same but alternate languages film versions which were filmed simultaneously, before his return to Italy.
He won Venice Film Festival Mussolini's cup for Best Italian Film twice, in 1936 by Lo squadrone bianco and in 1940 by The Siege of the Alcazar, both Fascist propaganda films.
In 1953, he filmed Three Forbidden Stories, another version of the real accident depicted by Giuseppe De Santis one year before in Rome 11 o'clock (Roma ore 11).