The younger brother of the eleventh Satsuma lord Shimazu Nariakira, Hisamitsu continued to hold real power over the domain as its effective father even after his nephew Tadayoshi became lord — despite never becoming lord himself. He was the most politically influential man in Satsuma during the Bakumatsu era. In 1862 he led a large army to Kyoto to demand personnel reforms from the shogunate (the Bunkyu Reforms), in pursuit of unity between court and shogunate. On the return journey that year, the Namamugi Incident occurred in a village near Yokohama, when his retainers killed a British national, leading to the Anglo-Satsuma War the following year. While restraining revolutionary Sonno Joi figures like Saigo Takamori and Okubo Toshimichi, he built up the domain's strength through the court-shogunate unity approach. After Saigo's defeat in the Satsuma Rebellion, he remained a leading figure of the conservative faction that strongly opposed abolition of domains and Westernization.

A power broker with conservative aristocratic tastes and intense drive for authority. He lacked the revolutionary vision of Saigo and Okubo, but his political instincts were sharp and he made a major contribution to building Satsuma's strength. His stubborn resistance to Westernization was also the limitation of his later years.

He led the strengthening of Satsuma domain during the Bakumatsu era, laying the groundwork for the Meiji Restoration. Known as a proponent of court-shogunate unity, Satsuma's drive toward modernization cannot be told without Hisamitsu's power diplomacy.