Nobumasa was born at the domain's Edo residence, and was received in formal audience by Shōgun Tokugawa Ienari in 1835.

Ii Naosuke was assassinated in the Sakuradamon Incident in 1860 and Andō Nobumasa became a leading councilor of state together with Kuze Hirochika.

He was instrumental in arranging for Kazunomiya, the younger sister of Emperor Kōmei, to marry Shōgun Tokugawa Iemochi.

British counsul-general Rutherford Alcock remarked on meeting the heavily-bandaged Andō shortly afterwards and was favourably impressed with his fortitude, stating that his injuries lent credence to claims by the shogunate that the opening of the country to foreign trade had to proceed slowly due to strong domestic opposition.

However, Andō was forced from office soon afterwards by his political enemies, who accused him of improper conduct in arranging for an heir to succeed Ii Naosuke and due to allegations that he had accepted bribes from American consul Townsend Harris.