Late in 1841, on the death of his foster-father (brother-in-law) he became daimyō of Sendai Domain, received the courtesy titles of Mutsu no Kami and Sakon-e gon-shosho.

The countryside was ravaged from the effects of enormous Tenpo famine, and for much of his tenure his actual income was much reduced, at times to even the 100,000 koku level.

However, traditional rivalries between the domains of eastern and western Japan, and the arrogant behavior of emissaries sent by the Satchō Alliance, such as Sara Shuzo forced Yoshikuni's hand, and he eventually became the somewhat reluctant leader of the Ōuetsu Reppan Dōmei.

However, because of Yoshikuni's indecisiveness and the confederation's incohesiveness and obsolescence of its weapons and tactics, Sendai Domain was defeated by the combined armies of the new Meiji government, led by Kujō Michitaka.

The same year, Yoshikuni's fourth son Date Munemoto succeeded as clan leader and was allowed to become daimyō of a much reduced Sendai Domain, with revenues of only 280,000 koku.