After experiencing many difficulties, he succeeded in completing a bachelor of law degree at the University of Oregon.
He returned to Japan in 1902 and in 1904, having passed the examination for diplomatic service, entered the Ministry of Foreign Affairs. He began his career with an assignment in Shanghai and later held posts in Russia and the United States. In 1919 he was appointed a member of the Japanese delegation to the Versailles Conference, being put in charge of relations with the press. In 1921 he retired from diplomatic service and became a director of the South Manchuria Railway Co. He left this position in 1926, and in 1927, at the request of Tanaka Giichi, the leader of the Seiyukai, he joined Yamamoto JStaro and others in a tour of China designed to ascertain the political situation there. After returning to Japan, he became vice-president of the South Manchuria Railway, lending valuable assistance to its president, Yamamoto Jotaro. He retired from this position in 1929. The same year, he attended the third meeting of the Institute of Pacific Relations held in Kyoto. There he clashed with the Chinese delegate over the Manchurian question and made an eloquent speech in English that won the admiration of Nitobe Inazo, the head of the Japanese delegation.
In 1930 he ran for election as an affiliate of the Seiyukai and was elected to the Lower House of the Diet as a representative from Yamaguchi Prefecture.
After his return to Japan, he withdrew from the Seiyükai and formed an organization known as the Seito Kaisho Remmei, or “League for the Dissolution of Political Parties.” He also resigned his seat in the Diet and set out on à lecture tour of thé country, calling for the dissolution of all political parties, cooperation on the international level with Germany and Italy, and the establishment of new world order. In 1935 he dissolved the Seito Kaisho Remmei and assumed the position of president of the South Manchuria Railway, but resigned in 1939. In 1940, in dissatisfaction over the foreign policy of the Yonai cabinet, he also resigned the position of cabinet councilor, which lie had held from the time of the Konoe cabinet in 1937. In the same year, he became minister of foreign affairs in the second Konoe cabinet and carried out a reshuffling of personnel in the Ministry of Foreign Affairs that came to be referred to as the “Matsuoka whirlwind.”
In the Diet, he spoke out against the peaceful diplomatic policy of Minister of foreign Affairs Shidehara Kijuro, reiterating the theme that "Manchuria and Mongolia are the lifeline of Japan!” .
He favored close cooperation with Germany and Italy and in 1940 succeeded in concluding the Tripartite Pact linking Japan with those two countries. He hoped, by gaining the cooperation of the Soviet Union as well, to form a coalition of countries that would enable Japan to settle her long-standing differences with the United States. He also formulated plans for Japanese expansion in Southeast Asia, outlining what came to be known as the Greater East Asia Coprosperity Sphere.