In 1858, when the 13th lord Iemochi TOKUGAWA (his given name was Yoshitomi in those days) assumed power as the 14th seii taishogun (literally, "great general who subdues the barbarians"), Mochitsugu succeeded Iemochi as the head of the Kishu Tokugawa Family by the order of the bakufu (Japanese feudal government headed by a shogun) and assumed a post of the 14th lord of the Kishu Domain.
安政5年（1858年）に第13代藩主・徳川家茂（当時は慶福）が第14代征夷大将軍に就任すると、幕命によりその後を受けて紀州徳川家の家督を継ぎ、紀州藩の第14代藩主に就任した。