During World War I, San Giorgio's activities were limited by the threat of Austro-Hungarian submarines, although the ship did participate in the bombardment of Durazzo, Albania, in late 1918.

She acted as a royal yacht for Crown Prince Umberto's 1924 tour of South America and then deployed to the Indian Ocean to support operations in Italian Somaliland in 1925–1926.

As part of her reconstruction, she received a modern anti-aircraft suite that was augmented before she was transferred to bolster the defences of Tobruk shortly before Italy declared war on the Allies in mid-1940.

[3] The main armament of the San Giorgio-class ships consisted of four Cannone da 254/45 A Modello 1908 guns in twin-gun turrets fore and aft of the superstructure.

Of the many targets, Ancona was hardest hit, with disruptions to the town's gas, electric, and telephone service; the city's stockpiles of coal and oil were left in flames.

When the Austrians resumed bombardments on the Italian coast in mid-June, Admiral Paolo Thaon di Revel responded by sending San Giorgio and the other armored cruisers at Brindisi—the navy's newest—to Venice to supplement the older ships already there.

[12] San Giorgio was relieved by the scout cruiser Brindisi as flagship of the Eastern Squadron on 16 July 1921 at Istanbul, Turkey.

[20] In 1937–1938 she was reconstructed to serve as a dedicated training ship for naval cadets at the Arsenale di La Spezia: six boilers were removed and the remaining eight were converted to burn fuel oil which reduced her speed to 16–17 knots (30–31 km/h; 18–20 mph).

[22] Two days after Italy declared war on Britain on 10 June, the British launched a co-ordinated sea and land attack against Tobruk.

[25] On 19 June, the British submarine HMS Parthian fired two torpedoes at San Giorgio, but they detonated before hitting the ship.

[26] San Giorgio's main role was to supplement the anti-aircraft defences of Tobruk; between June 1940 and January 1941, she claimed 47 enemy aircraft shot down or damaged.

[27][28] When Commonwealth troops surrounded Tobruk and prepared to storm it during Operation Compass, in January 1941, the ship was kept in port as it was thought that her main guns could be useful for halting, at least temporarily, the British tanks.

The ship was seaworthy (she had been stationary since June 1940, but she was not immobilized), and when the fall of Tobruk appeared imminent the local naval commander Admiral Massimiliano Vietina requested authorization from the naval high command in Rome (Supermarina) for her to leave, so as to avoid what was perceived as the preventable loss of a perfectly sound, if outdated, cruiser; however, the Italian commander-in-chief in Libya, Marshal Rodolfo Graziani, opposed San Giorgio's leaving, "…so as not to deprive the fortress of the contribution of San Giorgio’s guns and especially for moral reasons, since the departure of the ship would be harmful for the land troops' [morale] [if it were to happen] right at the moment the enemy attack is underway".

In the early hours of January 22, after the last resistance in Tobruk had ceased, the crew was disembarked and a small scuttling party, headed by Captain Stefano Pugliese, blew up her magazines so that she would not fall intact into British hands.

Most of the crew, including the badly wounded Pugliese (who had been injured by the premature explosion of one of the scuttling charges), were taken prisoner, although a small party managed to escape to Italy in a fishing boat, carrying with them San Giorgio's war flag.