In August 1894 he attended the Socialist congress for the Lombardy region, which was held in semi-clandestine fashion due to the repressive measures taken by Prime Minister Francesco Crispi.

During this time he was a strong advocate of support for Giovanni Giolitti, a liberal reformer, since he felt that this would allow Socialists to influence and contribute to progressive developments like the proposed introduction of universal suffrage.

In March 1912 he, along with other members of the right-wing of the Socialist Party, took the unprecedented move of meeting King Victor Emmanuel III to express their relief for the failure of an anarchist assassination attempt.

In June 1916 he was appointed Minister of Public Works in the Boselli cabinet and held this position for twelve months, until his resignation due to disagreements on domestic policy.

On 2 June 1943, he had a private audience with King Victor Emmanuel III where he proposed Mussolini's dismissal, the appointment of a military government, and the denunciation of the alliance with Nazi Germany.

During the same month Bonomi had other meetings with Maria José, Princess of Piedmont, and the heir apparent, Prince Umberto II, suggesting the appointment of Marshal Pietro Badoglio as prime minister with himself as his deputy, with the goals of ending both the Fascist dictatorship and the alliance with Adolf Hitler.

[3] After the fall of Fascism in July 1943, Bonomi attended a number of anti-fascist meetings which asked the new government led by Badoglio to disband Fascist organizations, release political prisoners, and restore the free press.

On 9 September, the day after the armistice of Cassibile was announced, six anti-fascist parties agreed to form a National Liberation Committee (CLN), chaired by Bonomi, to lead the Italian resistance movement.

Communists, Socialists and Actionists saw Victor Emmanuel III as complicit with Fascism and responsible for the disastrous wartime situation due to his attitude during both Mussolini's rise and the nearly twenty years of dictatorship, and demanded his immediate departure.

Christian Democrats and Liberals preferred to delay any discussion on the form of government to the end of the war, seeing the monarchy as a factor of legitimacy and national unity.

[3] Around the same time Enrico De Nicola also brokered a compromise solution where Victor Emmanuel would delegate his powers to the more palatable Prince Umberto, which the King accepted reluctantly.

[6] The main issues facing the new government were the prosecution of the war until the liberation of Italy from German occupation, as well as the practical implementation of various compromises that had been previously agreed on in principle.

As prime minister, Bonomi formally recognized the partisan forces operating in the North as part of the war effort, and organized them under a unified command led by Army general Raffaele Cadorna Jr., who was parachuted in the occupied areas.

[8] With the end of the war in Europe Bonomi started facing more frequent criticism over his personality and actions in the pre-Fascist era, particularly from politicians who had been living underground in the occupied areas and were close to the partisan movement.