Born on March 27, 1901, the third son of Sato Hidesuke and Moyo in Tabuse, Kumage District, Yamaguchi. His elder brother was Kishi Nobusuke (adopted into the Kishi family, hence a different surname). After Fifth Higher School he graduated from the German Law course of the Faculty of Law, Tokyo Imperial University (1924), and entered the Ministry of Railways. He distinguished himself as a railway bureaucrat, served as administrative vice-minister of transport in 1948, then in 1949 was promoted as chief cabinet secretary of the Third Yoshida Cabinet, entering politics. He went on to serve as minister of post and telecommunications, electrical communications, construction, finance, and international trade and industry, becoming the core of the Yoshida School. On November 9, 1964, succeeding Ikeda Hayato, he took office as the 61st prime minister. Through the 62nd and 63rd terms, three consecutive terms, he ran a long government of 7 years and 8 months (2,798 consecutive days) until July 7, 1972, setting the postwar Japanese record for longest consecutive prime ministership (later broken by Abe Shinzo). He concluded the Treaty on Basic Relations between Japan and the Republic of Korea in 1965; in a House of Representatives speech in 1967 advocated the Three Non-Nuclear Principles of 'not possessing, not producing, and not permitting the introduction of nuclear weapons'; signed the Okinawa Reversion Agreement on June 17, 1971; and on May 15, 1972, realized the reversion of administrative rights over Okinawa. In December 1974 he became the first Japanese to receive the Nobel Peace Prize for his achievements with the Three Non-Nuclear Principles and the reversion of Okinawa. On June 3, 1975, he suffered a cerebral hemorrhage at a restaurant in Tsukiji, Tokyo, and died on June 19 at 74.

Compared with his elder brother Kishi Nobusuke, an intellectual, Sato was a politician of human feeling and the coordinating type. Outwardly mild, he was excellent at the art of winning hearts, called 'niko-pon' (smile and pat on the shoulder). At the same time, as a former diligent and meticulous bureaucrat, he had the obsession to grasp policies down to the details and ran a long government. Called the politician of 'waiting' and of 'personnel,' he was characterized by patience that waited out rivals and never missed an opportunity. Easily moved to tears, he was famous for sobbing aloud before TV cameras at his resignation press conference.

The reversion of Okinawa is regarded as one of the greatest achievements of postwar Japanese diplomacy and decided Sato's historical evaluation. The Three Non-Nuclear Principles became the core of Japan's identity as a 'peaceful nation,' and the Nobel Peace Prize award established their international evaluation. On the other hand, diplomatic documents released in recent years have revealed the existence of a 'secret nuclear agreement' allowing the reintroduction of U.S. military nuclear weapons at the time of the reversion of Okinawa, and the divergence between the ideal of the Three Non-Nuclear Principles and reality has come under debate. Sato's long government was the longest in postwar Japan until Abe Shinzo broke the record, and during it national projects symbolizing Japan's prosperity — the Osaka Expo (1970), the opening of the Tomei Expressway and the Sanyo Shinkansen — were realized one after another. In Tabuse, Yamaguchi, an exhibition facility honors Sato Eisaku and Kishi Nobusuke.