[1] Kawanakajima in northern Shinano Province was the site of numerous battles in the Sengoku period between Takeda Shingen and Uesugi Kenshin.
In 1616, Matsudaira Tadamasa, the son of Yūki Hideyasu was awarded a 130,000 koku holding in northern Shinano, and chose Matsushiro as the location for his castle.
Following the establishment of the Tokugawa shogunate, Sanada Nobuyuki was confirmed as daimyō with Ueda Domain, with holdings assessed at 95,000 koku.
The Zenkoji earthquake of 1847 destroyed most of the town, and the domain's finances were depleted by demands from the shogunate for guard duty in Edo Bay against the return of Perry's "blackships".
Under the new Meiji government, Sanada Yukimoto, the last daimyo of Matsushiro Domain was given the kazoku peerage title of shishaku (viscount), and was later elevated to hakushaku (count).