The museum was founded on January 1, 1890, at the initiative of P. S. Mikhno, local merchants, exiles, and the Kyakhta intelligentsia. After the visit of the Potanin family to Kyakhta in 1890, a temporary committee was established to raise funds for the museum's maintenance, and the first exhibits began to appear. The first curator was P. S. Mikhno.

In 1892, with funds from merchant I. D. Sinitsyn, an apartment of 40 m² was rented and equipment for the museum was purchased. By 1893, the museum's collection numbered over 2,000 exhibits. Merchant A. D. Starcev donated a stone house to the museum, and the curator became teacher E. N. Sokolova.

Political exiles N. A. Charushin, Popov, Molleson, and Levin participated in the museum's creation. Due to resistance from the authorities, the museum did not have an approved charter and was not considered an official institution. In 1893, D. A. Klementz gave a lecture in Kyakhta on the tasks of local museums and proposed to open a branch of the Imperial Russian Geographical Society (IRGO). On July 13, 1894, a branch of the society was opened in Kyakhta, and the museum became its subdivision. The head of the IRGO branch was doctor Y. D. Talko-Gryntsevich. On January 1, 1895, the museum opened for visits on Sundays.

From 1894 to 1897, the IRGO branch and the museum conducted expeditions in southwestern Transbaikalia. The museum organized performances, concerts, and lectures. The formation of the collection involved V. A. Obruchev, D. A. Klementz, and P. K. Kozlov. Collections were gathered in various scientific directions, and items of Buddhist cult and everyday life were acquired in Mongolia.

By 1904, the museum's funds reached 14,000 units, and by 1911, 185 scientific works had been published. During World War I, the museum's scientific activity nearly ceased, and during the Civil War, the museum almost closed.

On January 31, 1922, the Government of the Far Eastern Republic transferred the museum to the Ministry of Public Education. The museum received funding, staff, and a two-story building constructed by merchant Nerpin in 1847. In the summer of 1921, P. S. Mikhno resumed scientific expeditions and became the curator again in April 1922.

After the formation of the Buryat-Mongolian ASSR, the museum came under the management of BURNARCOMPROS. As of January 1, 1924, the collection had 19,989 exhibits. In 1923, the museum was visited by 4,190 people, and 27 school excursions were conducted. The staff consisted of 5 people, so in 1924, a student local history circle was created. Since 1927, the circle published a magazine called “Sledopyt,” later renamed “Kyakhta Local History.”

In the summer of 1930, the museum explored the Borgoy Steppe, collecting a variety of flora and fauna samples. In 1931, the museum's collections grew to 50,000 units.

In 1940, on the 50th anniversary of the museum, it was granted republican status and named after Academician V. A. Obruchev. After the war, the museum organized local history circles and published the newspaper “For Soviet Science.”

In 1964, staff helped establish a local history museum in Sukhbaatar, Mongolia. In the 1970s, they worked on the Museum of the Mongolian People's Revolution in Altanbulag. In 1975, a branch of the Kyakhta Museum, the Decembrists Museum, opened in Novoselenginsk.

In 1981, a fund of rare books was allocated from the museum's library. In 1982, the Museum of Folk Art of the Peoples of Transbaikalia was established. In 1984, with the museum's participation, a folk museum opened in Sharagol.

In the 1980s and 1990s, the museum participated in archaeological research. In 1996, an International Congress of Archaeologists was held based on its premises.

In 2004, staff worked on creating the “Museum of Russian-Mongolian Friendship.” In 2009, they began excavations of the Hunnic burial ground Orgoyton in collaboration with archaeologists.

The museum conducts a Tea Ceremony with tastings of tea brewed according to ancient recipes, offering up to 8 types of tea.