The clan initially rose to prominence under Tōdō Takatora (1556–1630), who was a highly trusted commander under Hashiba Hidenaga, later Toyotomi Hideyoshi and Tokugawa Ieyasu, as well as an architect of numerous Japanese castles.

During the Bakumatsu period, the defection of the Tōdō clan to the Satchō Alliance in 1868 was a major factor in the defeat of the Tokugawa forces at the Battle of Toba–Fushimi.

The head of the clan was later awarded with the kazoku title of Count (hakushaku) by the Meiji government.

A junior branch of the clan, which ruled Hisai Domain in Ise Province (53,000 koku), was awarded the title of viscount (shishaku) in the Meiji period.

Another junior branch of the clan, which ruled Nabari in Iga Province (15,000 koku), was not styled as a daimyo, but was awarded the title of baron (danshaku) in the Meiji period.