Commissioned into service in the Italian Regia Marina ("Royal Navy") in 1915, she served in World War I, participating in the Adriatic campaign, including the Battle of the Strait of Otranto.

During the night of 11–12 December 1915 she and the destroyer Ardito escorted the steamships Epiro and Molfetta from Brindisi, Italy, to Durrës (known to the Italians as Durazzo) in the Principality of Albania, where the two steamers delivered supplies for the Serbian Army.

At 04:50 on 15 May, following news of these attacks, Simone Schiaffino, the Italian destroyer Rosolino Pilo, and the British light cruiser HMS Dartmouth made ready for sea to intervene in the clash.

Dartmouth, the British light cruiser HMS Bristol and the Italian destroyers Antonio Mosto and Giovanni Acerbi placed themselves between Aquila and the Austro-Hungarian ships and opened fire on them at 09:30 at a range of 8,500 metres (9,300 yd).

[3] An Austro-Hungarian Navy force consisting of Helgoland and the destroyers Balaton, Csepel, Lika, Orjen, Tátra, and Triglav left Cattaro on 18 October 1917 to attack Italian convoys.

[3] On 2 October 1918 Simone Schiaffino and Ippolito Nievo were at sea with the battleship Dante Alighieri, and the scout cruisers Alessandro Poerio, Carlo Alberto Racchia, Cesare Rossarol, and Gulglielmo Pepe to provide distant cover for a British and Italian naval bombardment of Durrës.

[6] On 24 April 1941, Simone Schiaffino was laying signal buoys in the waters of the Mediterranean Sea off Cape Bon, Tunisia, when her stern struck a mine that other Italian ships had just laid.