Sekiyado is located at the confluence of the Tone River and the Edogawa River, and was thus a strategic location controlling river traffic in the northern Kantō region, as well as the northeastern approaches to Edo. Following the Battle of Odawara in 1590, the Kantō region by was assigned to Tokugawa Ieyasu, who appointed his half-brother Matsudaira (Hisamatsu) Yasumoto as daimyō of Sekiyado, with revenues of 20,000 koku. His revenues were increased to 40,000 koku in 1591. The domain passed from Matsudaira control to various other clans over its history: however, as an indication of the importance the Tokugawa shogunate placed on Sekiyado, of the 22 daimyō who ruled the domain, 22 held the post of Rōjū and three held the post of Kyoto Shoshidai.
During the Boshin War, the domain officially remained a supporter of the Shogunate, and contributed many samurai to the Shōgitai; however, many of its younger retainers supported the Sonnō jōi movement and defected to the Satchō Alliance. After the Battle of Ueno, the final daimyō of Sekiyado, Kuze Hironari, submitted to the new Meiji government. He was appointed domain governor under the new administration, until the abolition of the han system in July 1871 and subsequently became a viscount under the kazoku peerage. The former Sekiyado Domain was absorbed into the new Chiba Prefecture.