Born in Mobara city, Kazusa Province (present-day Chiba Prefecture), Ishii graduated from the Law Department of Tokyo Imperial University and joined the Foreign Ministry. His first posting was as attache to Paris in 1891, and he was later sent to Korea in 1896 and to Qing Dynasty China in 1897. During the Boxer Rebellion he served as Japanese diplomatic liaison with the various foreign interventionist armies, spending six months on the front with the Imperial Japanese Army's 5th Infantry Division.
He became Vice Minister for Foreign Affairs under the 1st and 2nd Katsura administrations from 1908-1912. and after a term as ambassador to France from 1912-15, he became Minister for Foreign Affairs under the 2nd Okuma admnistration from 1915-16.
In 1917, he was nominated to the House of Peers. Ishii is remembered for his efforts to improve United States-Japan relations during a period of increasing tension over China, and the racist treatment of Japanese living in the United States. His approach reflected his strong belief that good relations between the United States and Japan were essential for Japan's future economic and political growth. As special envoy to the United States from 1917-1918, he negotiated the Lansing-Ishii Agreement, which was intended to defuse tension between the two nations, but was limited in its effectiveness due to the reluctance of either government to make any concessions. Ishii stayed on in the United States as ambassador from 1918-1919, attempting to reduce tensions created by the Siberian Intervention of Japanese forces into the Russian Far East as part of western support for White Russian forces against the Bolsheviks.
After his return to Japan, he served as a member of the Privy Council from 1925-1945, during which time he was highly outspoken in his strong opposition to the Tripartite Pact between Japan, Nazi Germany and fascist Italy.
During the third firebombing of Tokyo on 25 May 1945, Ishii was last seen heading towards Meiji Shrine, which was the designated safe refuge for his neighborhood association during the bombing. He never arrived, and he was presumed killed. His body was never found.