Nanbu Nobuyuki was born as the 14th son of Shimazu Shigehide, daimyō of Satsuma Domain.

In 1838, his adoption was official recognised in a formal audience with Shōgun Tokugawa Ieyoshi and he became daimyō of Hachinohe Domain in 1842 on the death of Nanbu Nobumasa.

During the Bakumatsu period, Nanbu Nobuyuki sided with the Tokugawa shogunate against the Satchō Alliance, and during the Boshin War, took his domain into the Ōuetsu Reppan Dōmei.

However, his allegiance to the Tokugawa clan over his own relatives in Satsuma was somewhat uncertain, and he maintained a secret diplomacy with pro-imperial Kubota Domain, which enabled the domain to survive the Meiji Restoration without loss of status.

He sold the former Hachinohe Domain's Tokyo residence to Princess Kazunomiya Chikako for the sum of 15,000 Yen in an attempt to rectify the clan's failing finances.