A number of influential persons in the early Meiji government came from Tsuwano, including Mori Ōgai and Nishi Amane.

Following the 1600 Battle of Sekigahara, the Tokugawa shogunate deprived the Mōri of two-thirds of their holdings, reducing the clan to the two provinces of Nagato and Suō.

Western Iwami became part of the 30,000 koku holdings of Sakazaki Naomori, one of Tokugawa Ieyasu's generals, who established his seat at Tsuwano.

His son Kamei Masanori, succeeded him at a young age, resulting in a succession dispute in 1635, but under the initiative of his karō, Tago Masakiyo , he managed the internal strife.

Through the middle of the Edo period, the clan's finances were prosperous, with washi paper being monopolized and new rice fields developed.