She participated in the normal peacetime activities of the fleet in the 1930s as a unit of the 2nd Squadron, including service in connection with the Spanish Civil War.

On 10 June 1940 she was part of the 4th Cruiser Division, with the 1st Squadron, together with her sister ship Alberico da Barbiano and was present at the Battle of Punta Stilo in July.

She carried out a minelaying sortie off Pantelleria in August, and for the rest of the year acted as distant cover on occasions for troop and supply convoys to North Africa.

Both she and her sister were being used for an emergency convoy to carry gasoline for the German and Italian mobile formations fighting with the Afrika Korps.

Alberto di Giussano was able to fire only three salvos before being struck by a torpedo amidships and hit by gunfire, which left her disabled and dead in the water.