Matsudaira Mitsuhisa was the younger son of Matsudaira Mitsutsune, the 8th "daimyō" of Matsumoto. In May 1842, he was proclaimed heir, and was received in formal audience with Shōgun Tokugawa Ieyoshi the same year. He became "daimyō" of Matsumoto Domain in 1845 on the retirement of his father. In 1861, he was appointed guard for Princess Kazunomiya for her travel through Shinano on the Nakasendō between Motoyama-juku and Shimosuwa-shuku on her way to Edo to marry the Shōgun. The following year, troops from Matsumoto were assigned to guard the British legation in Edo at the temple of Tōzen-ji; however, one of the "samurai" from Matsumoto, Ito Gunbei, was a member of the terrorists who attacked the legation the same year and was forced to commit "seppuku" for his role in the deaths of two Royal Marines. The same year, Matsumoto was also assigned to strengthen the guard of the defenses of Edo Bay at Uraga. Domain forces were also assigned to Kyoto in 1864 and fought on the Tokugawa side during the First Chōshū expedition. In 1868, just before the arrival of imperial troops into Matsumoto during the Boshin War, the domain capitulated and defected to the imperial side. Troops from Matsumoto subsequently fought for the Meiji government at the Battle of Hokuetsu and Battle of Aizu. Nevertheless, the domain was punished by a loss of 3000 "koku" from its "kokudaka" for its tardiness in supporting the Meiji government.