He held this post for most of World War II, until on 14 April 1943, Benito Mussolini, displeased with his "weak" repression of the workers' strikes that had taken place in northern Italy in March, dismissed him, replacing him with MVSN General Lorenzo Chierici.

[3][4][1][2] On 26 July 1943, Marshal of Italy Pietro Badoglio, the new head of the government, reinstated Senise in his position of Chief of the Police; after the Armistice of Cassibile and the start of Operation Achse, while the King, Badoglio and most of the government and military leaders fled to Brindisi, Senise remained at his post in Rome.

On 23 September 1943, he was arrested by SS Captain Erich Priebke in his office at the Viminale Palace, and was then transferred to Nazi Germany and imprisoned in the Dachau concentration camp.

[4][1][2] After his return to Italy, Senise was accused of aiding and abetting Fascism, but was acquitted by the Special Court of Assize in Rome.

In 1946, he published his memoirs, Quando ero Capo della polizia, 1940-1943, claiming he had tried to preserve the autonomy of the police with respect to the regime.