Born Isoroku Sadayoshi in the village of Kushigun Sonshomura on Hokkaido. He enrolled at the Naval Academy at Etajima, Hiroshima in 1896, graduating in 1904. In 1905 during the war with Russia he saw action as an ensign on the cruiser Nisshin in at the Battle of Tsushima against the Russian Baltic Fleet and was slightly injured. After the war he when with various ships all over the Pacific.
In 1913 he went to the Naval Staff College at Tsukiji, a sign that he was being groomed for the high command. Upon graduation in 1916, he was appointed to the staff of the Second Battle Squadron and was adopted by the Yamamoto family. From 1919-1921 he studied at Harvard University. Promoted to Commander apon his return to Japan he taught at the staff college before being sent to the new air-training centre at Kasumigaura in 1924 to direct it and to learn to fly. From 1926 to 1928, he was naval attache to the Japanese embassy in Washington. He was then appointed to the Naval Affairs bureau and made Rear Admiral, he attended the London Naval Conference in 1930. Back to Japan he joined the Naval Aviation bureau and from 1933 headed the bureau and directed the entire navy air program.
In December 1936, Yamamoto was made vice minister of the Japanese navy, from which position he argued passionately for more naval air power and opposed the construction of new battleships. He also opposed the invasion of Manchuria and the army hopes for an alliance with Germany, when Japanese planes attack a US gunboat on the Yangtze River in December 1937 he apologised personally to the American Ambassador. He became the target for right-wing assassination attempts, the entire Naval ministry had to be placed under constant guard. However on August 30, 1939 Yamamoto was promoted to full Admiral and appointed commander-in-chief of the entire fleet.
Yamamoto did not soften his logical anti-conflict stance, when the Japan signed the Tripartite Pact with Germany and Italy in September 1940, Yamamoto warned Premier Konoe Fumimaro not to consider war with the United States: "If I am told to fight... I shall run wild for the first six months... but I have utterly no confidence for the second or third year." He also accurately envisaged the "island-hopping" and air dominance tactics such a war would have. His foresight also led him to believe that a pre-emptive strike against US Navy forces would be vital if war did occur.
Following the invasion of Indochina and the freezing of Japanese assets by the US in July 1941, Yamamoto won the argument over tactics and when in December war was declared the entire First Fleet air arm under Admiral Nagumo Chuichi was directed against the American fleet at Pearl Harbor, attacking on December 7. With around 350 planes launched from six carriers, eighteen American warships were sunk or disabled. Unfortunately Nagumo's failure to order a second search-and-strike against the American carriers and Yamamoto's disinclination to press him turned a tatical victory into a strategic defeat.
Yamamato directed operations for the battle of Java Sea on February 27-28, 1942. Without airpower playing a significant role and fought almost entirely by cruisers the Japanese defeated a combined force of Dutch, British, and American ships, thereby enabling Japan to seize Java.
In April 1943, U.S. intelligence intercepted and decrypted reports of Yamamoto's inspection tour throughout the South Pacific. Eighteen American P-38 aircraft flew from Henderson Field, Guadalcanal to ambush Yamamoto in the air. On April 18, his transport aircraft was shot down near Kahili in Bougainville.