De Bono helped organize the Fascist Party during the early 1920s. In 1922, as one of the four Quadrumvirs, he organized and staged the March on Rome. This event signalled the start of the fascist regime in Italy. In the period following this, De Bono served as Chief of Police, Commander of the Fascist Militia, and, in 1925, Governor of Tripolitania, in Libya. De Bono was tried for his role in the assassination of the leftist politician Giacomo Matteotti, but was surprisingly acquitted.
In 1929, De Bono was appointed Minister of Colonial Affairs.
In 1935, De Bono continued to play an active part in the military and became the Supreme Commander of the Italian operation against Ethiopia during the Second Italo-Ethiopian War. On October 3, he led the advance of the Italian forces on the northern front and crossed into Ethiopia from Eritrea. On October 6, forces under De Bono retook Adowa and soon thereafter Axum. After these initial triumphs, De Bono's advance slowed appreciably. Mussolini quickly grew impatient with him and, by the end of November, De Bono was relieved of his command. His place was taken by MarshalPietro Badoglio. However, as compensation for his loss of command, De Bono was promoted to Marshal of Italy (Maresciallo d'Italia) on November 16. He also was appointed the Inspector of Overseas Troops.
In 1940, De Bono opposed the Italian entry into World War II. But he kept a low profile and, in 1942, he was appointed Minister of State. On July 24 and July 25, 1943, De Bono was one of the members of the Fascist Grand Council who voted to oust Benito Mussolini when Dino Grandi carried out a coup d'état. This led to the dictator's downfall, arrest, and imprisonment.
Later in 1943, Mussolini was rescued during the Gran Sasso raid and returned to power by Nazi Germany. He was set up by the Germans as the "Duce of the Nation" of a new Italian Social Republic (Repubblica Sociale Italiana, or RSI) in northern Italy. Upon his return to power, Mussolini had De Bono and others who voted against him arrested. He had them tried for treason. De Bono was convicted.
