The former Hosokawa landholding in Bizen was partitioned; Ogasawara Tadazane, who had ruled the Akashi Domain of Harima Province, was granted 150,000 koku of land in northern Bizen, with the territory's seat of government being placed at Kokura Castle. The secondary castle of Nakatsu became the center of the new Nakatsu Domain, which was granted to Tadazane's nephew Ogasawara Nagatsugu. Simultaneously, Tadazane's younger brother Ogasawara Tadatomo, who had been a hatamoto, was given Kitsuki Castle and the surrounding 40,000 koku worth of territory, making him a daimyo. Tadatomo retained rulership of Kitsuki until 1645, when he was moved to the Yoshida Domain of Mikawa Province.
Matsudaira Hidechika, the lord of the Takada Domain in Bungo Province replaced Ogasawara Tadatomo as lord of Kitsuki, being given a slightly reduced domain of 32,000 koku. His descendants ruled Kitsuki until the Meiji Restoration. As flatland was scarce in Kitsuki, land reclamation and industrial arts were encouraged; Hidechika brought around 100 peasants with him from Mikawa; they formed what became commonly known as the Mikawa-shinden farmland.
The domain's name spelling was changed in 1711, during the tenure of the third lord, Matsudaira Shigeyasu. Since then, it has been spelled 杵築. Kitsuki domain finances deteriorated due to the major famine in the Kyōho era; Miura Baien, a scholar then residing in the domain, was commissioned to solve the crisis. Among his reforms was the opening of the domain school, the Gakushūkan, in the Tenmei era (1781-1789).
Kitsuki was abolished along with the other Japanese domains in 1871, when it became . It was later absorbed into Ōita Prefecture, and the territory remains part of Ōita to the present day. The former ruling family were made shishaku (子爵) (viscounts) in the new kazoku nobility system in 1884.