Nobutsuna was born in 1596, the son of Ōkōchi Hisatsuna, a senior retainer of Tokugawa Ieyasu. He was adopted as the heir of his uncle, Matsudaira Masatsuna, in 1601. After being introduced to Hidetada and Ieyasu, he was appointed as page to Ieyasu's grandson Iemitsu. He was greatly admired by Iemitsu, and renowned within the Tokugawa administration for his sagacity. In the early years of his service, he was a hatamoto; he later became a daimyo. In 1623, he received the court title of Izu no Kami. He became daimyo in 1633, receiving the Oshi Domain as his fief. After the failure of Itakura Shigemasa to subdue the rebellion at Shimabara in 1637-38, Nobutsuna took command of the allied armies laying siege to Hara Castle, bringing the campaign to a successful conclusion. In his later years, he joined senior Tokugawa officials such as Hoshina Masayuki in supporting the underaged 4th shogun, Ietsuna.

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