Born in 1544, Nobesawa Mitsunobu was the son of Nobesawa Satsuma no Kami Mitsushige, first lord of Nobesawa Castle, and became its second lord. He held the Nobesawa silver mine within his domain and built his power on its operation. As a member of the "Eight Shields of Mogami" led by the Tendo clan, he fought Mogami Yoshiaki, lord of Yamagata Castle, for many years, often causing him great difficulty. In 1584, however, Yoshiaki won him over by marrying his own daughter Matsuo-hime to Mitsunobu's son Matagoro, and Mitsunobu surrendered — reportedly requesting, as a condition, that Yoshiaki spare the life of the Eight Shields' leader Tendo Yorizumi. Mitsunobu's defection caused the Eight Shields to collapse and Tendo Castle to fall, greatly advancing Yoshiaki's unification of Murayama district. That same year, when Yoshiaki destroyed Shiratori Nagahisa, lord of Yachi Castle, part of the conquered territory was granted to Mitsunobu. In November 1590 he accompanied Yoshiaki to the capital, and died of illness in Kyoto on March 14, 1591.

Known for his great strength and imposing physique, he was a formidable warrior who long troubled Mogami Yoshiaki, yet also showed a loyal streak in ultimately pleading for his former lord's life.

Sometimes counted among the "Four Guardians of Mogami," he was one of the clan's foremost warriors, whose economic strength from the Nobesawa silver mine and military power from his castle helped underpin Mogami Yoshiaki's unification of Murayama district.