After Mussolini took power in 1922, Bocchini was appointed by Deputy Minister Aldo Finzi as the Prefect of Brescia (1922–1923), then Bologna (1923–1925), and finally Genoa (1925–1926).

In 1926 Mussolini, on the advice of Luigi Federzoni (who knew him from Bologna), made Bocchini Rome's Chief of Police and de facto head of all civil law enforcement in Fascist Italy.

To achieve this, Bocchini was granted maximum political coverage, complete freedom of action and the privilege of reporting directly to Mussolini.

As Rome's Chief of Police, Bocchini oversaw the arrest and brutal treatment of many prominent anti-fascists, such as Antonio Gramsci, who died in April 1937, aged 45.

In two official visits, to Germany in 1936 and in 1938 to Italy, Bocchini and Himmler met to coordinate how the OVRA and the Nazis' Gestapo and Sicherheitsdienst could work internationally to share and gather intelligence and arrest political/ideological enemies.