The museum was founded in 1782 thanks to funds collected by the governor of the Irkutsk province, F. N. Klichka, among local nobles and merchants.

The initiators of the museum and library's creation were Academy of Sciences correspondent Alexander Karamyshev and honorary member of the Academy of Sciences Erik Laksman. The period of the museum's flourishing began with the opening of the Siberian branch of the Russian Geographical Society in Irkutsk in 1851, when the museum came under its management. At that time, the museum actively researched the Asian part of Russia through expeditions.

In 1879, a fire occurred in Irkutsk, destroying a significant part of the city, including the museum and library buildings. After the loss of 22 thousand museum exhibits and 10 thousand books, the museum was restored and reopened on October 6, 1883.

In 1896, at the Nizhny Novgorod All-Russian Exhibition, the museum was awarded a first-degree diploma.

In 1920, the museum of the All-Russian Society for the Protection of Nature was nationalized and became state property.

Today, the museum includes several departments: the history department, the nature department, the exhibition department "Window to Asia," the exhibition department "Museum Studio," the scientific and fund department, a library, and a children's museum center. The museum has a tour bureau that organizes bus tours around the city and its surroundings. The museum hosts exhibitions and displays that are visited by up to 300 thousand people annually.