Born in 1794 as the eldest son of Hamana domain lord Mizuno Tadamitsu, he became senior councillor in 1834, and in 1841 assumed leadership of the Senior Council to carry out the Tenpō Reforms. He issued frugality edicts covering the prohibition of luxury, price controls, and the regulation of morals; the Hito-kaeshi-rei (Return-to-Village Order) sent farmers who had flocked to Edo back to rural areas; and he ordered the dissolution of the merchant guilds. He also attempted through the Jōchi-rei (Land Cession Order) to make the domains of daimyo and hatamoto around Edo and Osaka into shogunate-administered lands, but met with fierce resistance from the daimyo and hatamoto, and fell from power in 1843. The Tenpō Reforms were the shortest-lived of the Three Great Reforms, ending in just over two years. He returned to the Senior Council in 1845 but fell from power again, dying in 1851 at age 58.

He had strong convictions and a passion for reform, but was also impulsive by nature and poor at political behind-the-scenes manoeuvring and compromise. Taking the Kansei Reforms of Matsudaira Sadanobu as his model, he aimed for a politics grounded in strict Confucian morality. He could not read the strength of the opposition and recklessly pushed through the Jōchi-rei, in a sense bringing about his own downfall.

The Tenpō Reforms are recorded in history as one of the Three Great Reforms of the Edo Shogunate, but they are also discussed as a lesson in failure as the shortest-lived of the three. The dissolution of the merchant guilds disrupted economic activity and price controls also proved ineffective. The backlash against the Jōchi-rei is assessed as an event that clearly demonstrated the collapse of shogunal authority. The failure of the Tenpō Reforms is an important turning point leading to the decline of the shogunate in the late Edo period.