He was promoted to rank of captain in 1917, and remained on active duty in the Italian Army until 1923 – in the meantime, he earned his bachelor's degree in law from the University of Pisa in March 1920.

A mayor of Pisa in April 1923, Buffarini Guidi headed the local Party hierarchy from 1924 (his notoriety being increased by his career as a lawyer).

In May 1933, he was appointed to be Undersecretary Minister of Interior, and forged an alliance with Galeazzo Ciano - opposing the Party bureaucracy, creating several secret services, and attempting to lessen the effects of Antisemitic legislation passed by the regime.

Nevertheless, (and unlike Ciano), on 25 July 1943, Buffarini Guidi voted in favor of Benito Mussolini during Dino Grandi's attempt to have the latter deposed and get Italy to sign a peace with the Allies.

He was executed by firing squad on 10 July, having tried (like French collaborator Pierre Laval) and failed to commit suicide while in captivity.