Born in Tokyo on September 22, 1878, the fifth son of the Freedom and People's Rights activist Takeuchi Tsuna, and adopted by the Yokohama trading merchant Yoshida Kenzo. After graduating from the Political Science Department of the Faculty of Law, Tokyo Imperial University, he entered the Foreign Ministry and served as consul-general in Mukden, ambassador to Italy, and ambassador to Britain. During the war he was involved in peace work and was detained by the military police in 1945. After the war he became foreign minister in the Shidehara Cabinet and in May 1946 took office as the 45th prime minister. He served as the 48th, 49th, 50th, and 51st prime minister, in all five terms totaling about seven years. On September 8, 1951, he signed the San Francisco Peace Treaty and the Japan-U.S. Security Treaty, laying the foundation for Japan's recovery of independence and for the Japan-U.S. alliance. He stepped down in December 1954 over the shipbuilding scandal and conflict with Hatoyama Ichiro. After retiring from politics, from his Oiso home he retained political influence known as 'Oiso pilgrimages,' producing prime ministers from the 'Yoshida School' such as Ikeda Hayato and Sato Eisaku. He died at Oiso on October 20, 1967, at 89, and was given the first postwar state funeral.

A strong personality called the 'One-Man Premier.' Fond of cigars, he toyed with political rivals through sharp tongue, irony, and humor. He liked British-style dandyism and was known for a distinctive figure in white tabi and cane. He would shout 'bakayaro' at aides but also doted on his grandson Aso Taro, showing a rich human side. As a career diplomat he had an excellent international sense and held to the 'Yoshida Doctrine' of light armament and emphasis on the economy.

Yoshida's line of 'light armament and emphasis on the economy' became the basic state policy of postwar Japan and laid the groundwork for the era of high growth. The Japan-U.S. security system remains the axis of Japanese diplomacy today, and evaluation of the Yoshida Doctrine continues. Prime ministers from the 'Yoshida School' — Ikeda Hayato, Sato Eisaku, Miyazawa Kiichi, and Aso Taro (his grandson) — later formed the conservative mainstream of the Liberal Democratic Party. The site of his Oiso residence is open to the public as the 'Former Yoshida Shigeru Residence District' in Oiso Shiroyama Park. His 1967 state funeral was the only one in the postwar period and became the precedent for debate over the state funeral of Abe Shinzo in 2022.