A law graduate (1870) and an ardent republican, Cambon served as secretary to the future statesman Jules Ferry (Ferry, Jules), then mayor of Paris. Sent to the département of Bouches-du-Rhône as secretary-general of the prefecture (April 1871), he later served in several other départements.

In February 1882 Ferry arranged for Cambon's appointment as resident minister in Tunisia, where he successfully organized the French protectorate. After his ambassadorship to Spain (from August 1891), he was transferred to Turkey, but he failed in his efforts to negotiate a British withdrawal from Egypt. In August 1898, amid the severe tensions of the Fashoda crisis, Cambon became ambassador to Great Britain. His first years there were spent in smoothing over Anglo-French relations and were crowned by the signing of the agreement of April 8, 1904, often called the Entente Cordiale. Its immediate effect was to strengthen France's position in its conflicts over Morocco (1905–06 and 1911) with Germany, and in the long run it prepared the way for the alliance against the Central Powers in World War I. During that war Cambon continued to play a vital role in cooperation between the two allies. After service as a representative on the Turkish commission of the Versailles Conference (February 1920), he resigned his ambassadorship (December 1920) and in retirement was elected to the Academy of Moral and Political Sciences.