Guzzoni joined the Italian Royal Army (Regio Esercito Italiano) and fought in World War I.

After the Second Italo-Abyssinian War, Guzzoni was appointed Governor of Eritrea.

In June 1940, after Italy entered World War II, Guzzoni commanded the Italian 4th Army during the invasion of France.

On 29 November 1940, Guzzoni succeeded Ubaldo Soddu as Under-Secretary of War and Deputy Chief of the Supreme General Staff.

After the Italian armistice of September 1943, Fascist republican soldiers captured general Guzzoni, but he avoided execution thanks to the help of some German officers who appreciated his role during the defense of Sicily.