The domain was centered at Takada Castle, located in what is now part of the city of Jōetsu in Niigata Prefecture.
After Toyotomi Hideyoshi relocated Uesugi Kagekatsu to Aizu, he assigned the area to one of his generals, Hori Hideharu, who had distinguished himself in various battles.
He was replaced by Matsudaira Tadateru, the 6th son of Tokugawa Ieyasu, who built Takada Castle.
This also served to strengthen the position of the shogunate against the powerful tozama Maeda clan of Kanazawa Domain.
A junior branch of the Sakai clan briefly ruled Takada from 1616 to 1618, followed by Matsudaira Tadamasa from 1619-1623.
Takada was then assigned to a junior branch of the Hisamatsu-Matsudaira clan, who ruled uneventfully from 1710 until their transfer to Shirakawa Domain in 1741.
The head of the Sakakibara clan was ennobled with the title of viscount in the kazoku peerage system.
Masazumi was the eldest son of Sakakibara Masamine, and became daimyō in 1741 on the forced retirement of his father, who had angered Shōgun Tokugawa Yoshimune by flaunting sumptuary edicts, and purchasing the freedom of Takao Daiyu, a famed courtesan from a Yoshiwara brothel for a tremendous sum of money.
Yoshimune further punished Masamine by ordering the transfer of the clan from Himeji to Takada, which, although it had the same nominal kokudaka, was remote and cold and had a portion of lands spread over a number of exclaves in Mutsu Province.
This placed the domain in grave danger of attainder, as without having been formally acknowledged, the clan could not maintain the succession through a posthumous adoption.
Masazumi died in 1745 at age 10 before having been received in audience by the Shōgun, so then clan kept the death secret and renamed Masanaga to take his place.
His tenure was uneventful and his received promotion to Junior 4th Court Rank in 1754 and the additional courtesy title of Jijū in 1784.
He was noted as an outstanding ruler, reforming the domain's finances, ordering all of his samurai to plant fruit trees in their gardens, improving crop yields and developing onsen.
At the end of the war, many Aizu samurai were sent as prisoners to Takada, but were treated well by a largely sympathetic populace.