Born the fourteenth son of the Hikone domain lord, he spent many years as a 'room-dweller' in modest quarters he named 'Umoreginosha' (House of the Buried Tree). During those difficult years he devoted himself to tea ceremony, national learning, poetry, and martial arts, deeply internalizing the tea spirit of 'ichigo ichie' (cherish each encounter as once in a lifetime). After his brothers' deaths he became domain lord at thirty-two and was appointed Tairo—the shogunate's highest office—in 1858. Amid the chaos following Perry's arrival, he signed the Harris Treaty without imperial sanction, opening Japan to foreign trade. In the shogunal succession dispute he backed Yoshitomi (Iemochi) and ruthlessly suppressed opponents—including Mito and Satsuma domain factions who favored Hitotsubashi Yoshinobu—in the Ansei Purge, punishing over a hundred people and executing Yoshida Shoin, Hashimoto Sanai, and other loyalist figures. Resentment over this authoritarian rule led seventeen samurai to assassinate him outside Sakuradamon Gate on March 3, 1860. He also left the world the concept of 'ichigo ichie' and the tea treatise 'Chayu Ichi-e Shu.'

A cultured man versed in tea ceremony who coined "ichigo ichie" (once in a lifetime), yet showed iron resolve in politics. His strong will was his strength, but suppressing dissent ultimately cost him his life.

His decision to open Japan ultimately paved the way for modernization, though the Ansei Purge fueled anti-shogunate sentiment. His concept of "ichigo ichie" remains a defining principle of Japanese culture.