A member of an old noble family active in national politics, the young San Giuliano received his law degree in 1875, achieved local office in 1879, and, in 1882, became the youngest member of the Chamber of Deputies. His interests there centered on colonization and foreign affairs.
In 1899/1900 he obtained his first Cabinet portfolio as minister of posts and telegraphs. In 1904, however, he was defeated for reelection to the Chamber. The marquis then entered on a diplomatic career. He managed to begin at the top; in the winter of 1905/1906 he directed the Foreign Ministry for several months. From 1906 to 1910 San Giuliano was a popular and successful ambassador to London. In early 1910 he was posted to the Paris embassy. San Giuliano barely had time to settle in when, in March, he was called to Rome to lead the Foreign Ministry for the second time. During the next four and a half years, the marquis was Italy's only foreign minister.
The job required a master of cynical caution. Italy's diplomatic shelter against Europe's gathering storms was the Triple Alliance. But membership in that alliance meant association with Germany, whose power Italy not only needed but feared. It also meant a link with Austria-Hungary, and Vienna's expansionist designs on the Balkans continually threatened to spark a war of unpredictable dimensions. The situation was further complicated by growing public hostility in Italy toward Austria-Hungary. Italian irredentists bemoaned the fate of their brothers under Austrian control. San Giuliano was interested in expanding Italian influence in areas like Albania, but since that was likely to encourage Austrian expansionism, he found it desirable to be satisfied with the status quo in the Balkans. He was, in any case, certain that any Austrian gains in that sensitive area must be accompanied by territorial acquisitions by Italy, specifically, Trieste, otherwise Italian public opinion was likely to explode.
San Giuliano's policy in the July crisis of 1914 proceeded along several intertangled lines. To restrain Austria from making demands on Serbia was probably the best hope, but hardly a realistic one. To match Austrian gains with reciprocal gains in territory for Italy was next best. But many Italians were unlikely to accept the sight of Italian soldiers fighting side by side with the Austrian army, and that was the only way to make Austria generous in granting territory to Rome. San Giuliano tried to forestall the worst possibility, which was a set of Austrian gains with no compensation whatsoever to Italy.
He hinted until August 1 that Italy might indeed honor the Triple Alliance in this instance, but the Austrians insisted on actions not just words. In the end, San Giuliano chose the expedient of neutrality, which he saw as his country's best stance until the drift of military events became clear.
For the remaining few months of his life, San Giuliano watched the evolution of the war; and he attempted to match his diplomatic maneuvers with the rising and falling prospects of each side. This meant, for example, striving to better relations with the Central Powers in late August, as German armies poured through Belgium toward a likely victory in northern France. Conversely, it meant tilting toward the Entente in the aftermath of the battle of the Marne. San Giuliano got nowhere, however, with his request to bring the Allied navies into the Adriatic so that Italy's war effort could begin in the aftermath of the capture of Trieste by the Anglo-French fleet.
San Giuliano died in Rome on October 16, 1914. The war was less than three months old. But Italy's first wartime foreign minister had set an important pattern: watchful waiting; sizing up the prospects of each side for a quick military victory; weighing the generosity of the two rival alliances in rewarding Italy for its intervention in the conflict.