Quarto was based at Brindisi during World War I; she saw action once, during an attack by the Austro-Hungarian Navy on transports operating in the southern Adriatic.

Quarto served briefly in East Asian waters in the early 1930s, and supported Italian forces during the Second Italo-Abyssinian War in 1936.

The following year she served as the flagship of the Italian forces participating in the non-intervention patrols during the Spanish Civil War; here she was attacked by Republican bombers, although she escaped damage.

She was stricken from the naval register in January 1939 and subsequently used in weapons tests with human torpedoes and explosive motorboats.

At the same time, the development of more effective fire-control systems allowed ships to fight at longer ranges, and tactical developments identified during the recent Russo-Japanese War (specifically the concept of crossing the T) led to the need for high-speed fleet scouts so that commanders could maneuver their fleet more effectively.

The Austro-Hungarians developed the light cruiser Admiral Spaun to fill this need, which prompted the Italian response with Quarto.

[3][a] Quarto was reported to have had seakeeping qualities; the contemporary journal The Marine Engineer and Naval Architect observed that it was likely the result of the ship being overloaded for her size, and noted that the problem also afflicted the subsequent Nino Bixio-class cruisers.

Admiral Paolo Thaon di Revel, the Italian naval chief of staff, believed that Austro-Hungarian submarines could operate too effectively in the narrow waters of the Adriatic, which could also be easily seeded with minefields.

Instead, Revel decided to implement blockade at the relatively safer southern end of the Adriatic with the main fleet, while smaller vessels, such as the MAS boats, conducted raids on Austro-Hungarian ships and installations.

[10] Quarto was based at Brindisi in southern Italy to support the Otranto Barrage, along with the protected cruisers Puglia, Nino Bixio, and Libia, and several destroyers and submarines.

[11][12] During the war, enemy submarines frequently misjudged Quarto's speed as a result of her very shallow draft, which produced a misleading wave pattern on the hull.

[2] On 29 December 1915, an Austro-Hungarian force of two cruisers and five destroyers attempted to intercept transports supplying the Serbian Army trapped in Albania.

Quarto, flying the flag of Rear Admiral Silvio Bellini, and the British cruiser HMS Dartmouth, along with five French destroyers, sortied from Brindisi to intercept the Austro-Hungarians.

Quarto and Dartmouth pursued the cruiser SMS Helgoland and fought a long-range gun battle as the Austro-Hungarian ship tried to escape.

[13][14] Poor coordination between the Italian, British, and French ships led to their failure to decisively engage the Austro-Hungarians, but the latter nevertheless lost two of their six best destroyers.

[2] She thereafter served as the flagship of Rear Admiral Alberto di Moriondo, the commander of Italian warships operating off Spain with the non-intervention patrols during the Spanish Civil War.

The ship suffered a boiler explosion while moored in the Port de Pollença, Majorca, on 1 August 1938, which killed seven men.

[2] These tests included a trial of the new SLC human torpedo, which was later used by the Decima Flottiglia MAS, in La Spezia in early 1940.