According to Nanbu clan tradition, Mitsuyuki was born as the third son of Kagami Tomitsu (his birth year is uncertain, with 1165 among the traditional dates given). He is said to have followed Minamoto no Yoritomo at the Battle of Ishibashiyama in 1180 and taken the Nanbu surname from Nanbu Pasture in Kai Province (present-day Nanbu, Yamanashi). The Nanbu clan chronicle Onan Kyushiroku claims that in recognition of his service in the 1189 Oshu campaign, Yoritomo granted him the five districts of Nukanobu in Mutsu Province; he is said to have entered the region around 1191 and built Heragasaki-date the following year as his administrative seat. However, because the Nanbu clan does not appear in the 1275 construction records of Kyoto's Rokujo Hachiman Shrine, historians have suggested that the clan's actual advance into Mutsu may not have occurred until the late Kamakura period, meaning the traditional account of Mitsuyuki's grant and castle-building may be a later clan legend. He is said to have died in 1236. The Nanbu clan he founded later branched into numerous houses — including the Sannohe, Hachinohe, and Shichinohe lines — that expanded across northern Mutsu and Dewa, and continued into the Edo period as the ruling families of the Morioka and Hachinohe domains.

Though the historicity of the traditional account is debated, Nanbu clan lore portrays him as a pioneer who opened up the Nukanobu region through loyal service to Minamoto no Yoritomo. As his descendants branched into a wide network of houses across northern Oshu, he came to be revered in later generations as the symbolic founding ancestor binding the clan together.

The Nanbu clan that traces its founding to Mitsuyuki maintained power across northern Mutsu and Dewa through numerous branch houses, including the Morioka and Hachinohe domains, until the end of the Edo period. Heragasaki-date in present-day Nanbu Town, Aomori, traditionally said to have been built by Mitsuyuki, is still cherished locally as the legendary birthplace of the clan.