He became Chief of the 3rd Section of the Imperial Japanese Navy General Staff in December 1926. Within the Navy General Staff, he served on the Technical Council of the Navy Technical Department.
He was appointed Commander-in-Chief of the First Expeditionary Fleet, sent to the Yangtze River in China in December 1928. Following the success of this mission, he was promoted to vice-admiral in December 1930 and placed in command of the Chinkai Naval Station, in Korea.
Yonai was given command of the IJN 3rd Fleet in December 1932, following which he again commanded the Sasebo Naval District (November 1933), IJN 2nd Fleet (November 1934) and Yokosuka Naval District (December 1935) before receiving appointment as Commander-in-Chief of the Combined Fleet and concurrently the IJN 1st Fleet in December 1936.
While in command at Sasebo, the Japanese Navy was shaken by the “Tomozuru Incident”, when it was determined that the basic design of the Chidori-class torpedo boats was flawed, thus calling into question the basic designs of many of the warships in the Japanese navy.
While in command at Yokosuka, the February 26 Incident erupted in Tokyo. Yonai was visiting his mistress in Shimbashi the night the attempted coup d'État began, only a couple of blocks away, but knew nothing of the situation until he returned to base the following morning.
Yonai became full admiral in April 1937 and Navy Minister in the cabinet of Prime Minister Senjuro Hayashi in 1937. He served in the same position under the subsequent first Fumimaro Konoe and Kiichiro Hiranuma administrations, through August 1939.
After Nobuyuki Abe became Prime Minister, Yonai remained on the Supreme War Council. While Navy Minister, Yonai was known as a man of few words. His speeches tended to be short, and were delivered in his almost indecipherable Nambu accent. Written records of his speeches are only about half the length of his contemporaries.
As Navy Minister, Yonai was alarmed by the growing tension between Japan and Great Britain and the United States, at a time when the bulk of the Imperial Japanese Army was tied down in an apparently unending quagmire in China. His efforts to promote peace made him unpopular with ultranationalist extremists, and (as with Admiral Isoroku Yamamoto), he was the target of several assassination attempts. However, Yonai supported the construction of the Yamato class battleships in an effort to maintain a military balance with the world’s other two naval superpowers.
Yonai was appointed Prime Minister of Japan from 6 January 1940, largely with the backing of Emperor Hirohito. As Prime Minister, he continued the strong pro-British, pro-American stance he held as Navy Minister and continued his strong opposition to the Tripartite Pact with Nazi Germany and fascist Italy.
Yonai remained Navy Minister under the administration of Prime Minister Kantaro Suzuki. In the last few weeks before Japan's surrender, he sided with Prime Minister Suzuki and Foreign Minister Shigenori Togo in support of acceptance of the Potsdam Declaration in opposition to Minister of War Korechika Anami, Chief of Staff Admiral Soemu Toyoda and General Yoshijiro Umezu.
Yonai remained Navy Minister in the cabinets of Prime Minister HIH Higashikuni Naruhiko and Prime Minister Kijuro Shidehara from August 1945, during which time he presided over the final dissolution of the Imperial Japanese Navy.
He played a major role during the Tokyo war crimes trials in working with the major defendants, such as Hideki Tojo, to coordinate their testimonies so that Emperor Hirohito would be spared from indictment. According to his interpreter Suichi Mizota, in March 1946 Bonner Fellers asked him to make Tojo bear all responsibility for the Greater East Asia War After the war, Yonai devoted rest of his life to help to rebuilt the devastated Japan.