[3] As a Liberal he was elected a deputy for the first time in 1909 and, from 1913 to 1921, he filled minor governmental posts until the advent of fascism, when he retired from political life.

After Benito Mussolini's fall from power in 1943, king Victor Emmanuel tried to extricate the monarchy from its collaboration with the Fascist regime; De Nicola was perhaps the most influential mediator in the ensuing transition.

A new Constituent Assembly was elected, and prime minister Alcide de Gasperi became acting head of state for a few weeks when Umberto II was exiled and left Italy.

Giulio Andreotti later recalled that De Nicola — a man of great modesty — was not sure whether to accept the nomination and underwent frequent changes of mind in the face of repeated insistence by all the major political leaders.

Andreotti recalled that the journalist Manlio Lupinacci then issued an appeal to De Nicola in the pages of Il Giornale d'Italia: "Your Excellency, please, decide to decide if you can accept to accept...."[5] On 25 June 1947, De Nicola resigned from the post, citing health reasons, but the Constituent Assembly immediately re-elected him again the following day, having recognized in his act signs of nobility and humility.