Born in Mino Takasu Domain, he was adopted by Matsudaira Katayuki, lord of Aizu Domain. In 1862 the shogunate ordered him to serve as Protector of Kyoto; he organized and commanded the Shinsengumi to maintain public order. He supported the unity of court and shogunate and cracked down on radical sonnō jōi activists, and in the Kinmon Incident of 1864 he fought to defend the imperial palace. He continued to oppose the Satsuma-Choshu-led movement to overthrow the shogunate and enjoyed the deep trust of Emperor Komei. However, after Emperor Komei's death in 1866 his position weakened, and in the Boshin War of 1868 he was branded a court enemy. He made a stand in Aizu-Wakamatsu Castle and fought the Meiji forces, but at the cost of many samurai and civilians—including the Byakkotai—and surrendered on September 22, 1868. He spent his remaining years as chief priest of Nikko Toshogu Shrine, and died at fifty-eight on December 5, 1893. The people of Aizu still deeply revere him as 'the Righteous Lord,' and the tragedy of Aizu is passed down across generations. As the commander of the Shinsengumi, he stands out as a figure of particular presence in modern Japanese history.

A sincere warrior who placed great value on duty and loyalty. He faithfully carried out the duties of the Protectorship of Kyoto he had been ordered to discharge and remained loyal to the shogunate to the very last. He accepted the stigma of 'court enemy' without flinching and never changed his stance.

He continues to be remembered by many as an important Bakumatsu figure who commanded the Shinsengumi and as a symbol of the tragedy of Aizu. Tsurugajo (Aizu-Wakamatsu Castle), closely associated with Lord Katamori, attracts many visitors as a historic site.