The Smolensk State Museum-Reserve, one of the largest museum associations in Russia, is located in Smolensk. It consists of 12 exhibition departments in the city and 5 branches in the region. This association was formed based on three museums: the Historical and Archaeological Museum, the Historical and Ethnographic Museum, and the Natural History Museum. Each of them was established at different times and represented various forms of organization: under the city council, based on a private collection, and through a public organization.

The oldest is the Historical and Archaeological Museum, opened in June 1888 in the basement of the city council building by local historian S. P. Pisarev, who became its first director. The museum's opening coincided with the visit of Grand Duke Vladimir Alexandrovich and his wife Maria Pavlovna to Smolensk. The core of the collection consisted of ancient building materials from Pisarev and a collection of antiquities from historian V. I. Grachev. In 1912, the museum was transferred to the branch of the Moscow Archaeological Institute. Its activities were interrupted during World War I and the 1917 revolution, and the collection remained packed for evacuation, which did not take place.

In June 1898, Princess Maria Klavdievna Tenisheva opened the "Skrynya" museum in her estate Talashkino with a collection of Russian antiquities, which became the foundation of the "Russian Antiquities" museum. In the early 20th century, when the exhibition required expansion, the princess built a two-story building designed by S. V. Malyutin. In 1904, the collection moved there. Due to concerns for the safety of the exhibits during the first Russian revolution, the collections were transported to Paris, where they gained recognition. In 1908, the collection returned to Russia, and in 1909 the museum reopened. In 1911, Tenisheva transferred the museum to the Moscow Archaeological Institute. In 1912, the museum was visited by Nicholas II, and it was renamed the "Historical and Ethnographic Museum of the Imperial Moscow Archaeological Institute." In 1915, the museum was closed due to the approaching military actions, but the evacuation of the collection did not take place.

The Natural History Museum was founded in 1908 by scientists G. L. Grave and Ya. Ya. Alekseev and other members of the "Society for the Study of Smolensk Province." The museum did not have a permanent location and frequently changed its address, but it remained the only one that did not cease operations during World War I and the October Revolution.

In 1920, all museums were united into a single provincial museum. In the following years, its name and structure changed multiple times. Since 2011, it has been the Regional State Budgetary Institution of Culture "Smolensk State Museum-Reserve." The museum's funds contain over 600,000 items housed in 4 buildings. There are 14 collections, including archaeology, painting, graphics, sculpture, decorative and applied arts, ethnography, textiles, natural science collections, weapons and military equipment, numismatics, furniture, photographs, documents, rare books, and items made of precious metals.

In 2013, the museum-reserve joined the international project "Russian Museum: Virtual Branch," opening an information and educational class and a multimedia cinema in its departments as an electronic equivalent of the Russian Museum collection.