A member of the House of Representatives from 1946 to 1947 and 1952 to 1972, he served in several cabinet positions throughout his career, such as Deputy Prime Minister under Nobusuke Kishi.

Ishii was childhood friends with Shojiro Ishibashi, the founder of Bridgestone, and the two men remained close all their lives.

In January 1947, Ishii joined the cabinet of Shigeru Yoshida as Minister of Commerce and Industry, but in May he was purged from public office by the GHQ.

He served briefly as the first president of the Asahi Broadcasting Corporation from 1951 to 1952, but when the purge had been lifted, he returned to political life in the 1952 general election.

[1][7] In May 1960, at the height of the massive Anpo protests against the US-Japan Security Treaty, Ishii banded together with fellow faction leaders Ichirō Kōno, Kenzō Matsumura, Takeo Miki, and Ishibashi Tanzan to try to bring down the Kishi cabinet in response to Kishi's mishandling of the protests and especially his unpopular way of ramming the treaty through the Diet in the "May 19 Incident".

[8] When Kishi finally resigned in disgrace in July 1960, Ishii ran in the leadership election to replace him.

Most of the faction heads who did not support Ikeda came to rally behind Ishii, including Banboku Ōno, Ichirō Kōno, Kenzō Matsumura, and Takeo Miki.

Thus, Ikeda prevailed in the end, but he still made Ishii Minister of International Trade and Industry in his first cabinet as a gesture of reconciliation.

Ishii returned to the cabinet under Ikeda's successor Eisaku Satō as Minister of Justice from 1965 to 1966.

Their eldest son, Kōichirō, was employed at the Bridgestone Corporation founded by his father's friend Shojiro Ishibashi.