The museum was founded by Mikhail Alekseevich Radishchev, the great-grandson of the writer A.N. Radishchev, who served as a city judge. In the late 19th century, he collected a private museum collection, including collections of cold and firearms, numismatics, ethnography, and ornithology, which became the Khvalynsk Natural History Museum in 1919.

The museum is located in the city center and occupies two buildings. The history department is housed in an old two-story mansion from the early 19th century, which belonged to M.A. Radishchev. It was here that he opened the first public museum in Khvalynsk in the late 19th century.

On the second floor of the mansion, accessed by a grand staircase, are the memorial rooms, a buffet, and the owner's study, which recreate the atmosphere of the past. Other halls feature exhibitions of merchant life and collections of icons, old printed and handwritten books, and church utensils from the Cheremshansk Old Believer monasteries, which were the last stronghold of the old faith in the Volga region in the early 20th century. The ceiling stucco, doors, and other interior elements have been preserved in their original form, which, combined with the successful wall colors, creates a sense of authenticity.

On the first floor of the mansion, there are exhibitions about the history of Khvalynsk. The archaeological collection spans from the Paleolithic to the Middle Ages. Here you can see rarities such as items from the Staro-Yablonsk Eneolithic burial ground and a Neanderthal skull cap, the seventh such find in the world. Evidence of local metalworking is shown by a hoard of bronze items from the village of Sosnovaya Maza, part of which was transferred to the State Historical Museum.

The exhibition covers all eras and cultures up to the late nomads, including the Golden Horde. Khvalynsk was founded as a watch post on Sosnovy Island and was moved to the right bank in 1685. Exhibits such as fishing gear and weapons provide insight into the lives of the first settlers.

In 1780, Catherine II transformed the village into the city of Khvalynsk, likely named after the nomadic tribes of the Khvalis. The ethnographic collection illustrates the history of the region's settlement and its ethnic composition, including Mordovian and Chuvash costumes and Tatar jewelry. A separate exhibition is dedicated to the daily life of Khvalynsk residents at the turn of the 19th-20th centuries and unique Old Believer relics.

The nature department is located in a building constructed in 1977 with the assistance of M.A. Suslov. The interior is lined with limestone and dolomite, as well as marble onyx found in the Berezovsky quarry. The building originally housed an exhibition from the Soviet period.

M.A. Radishchev's ornithological collection includes about 250 specimens and was personally collected by him. Most of the collection consists of local bird species that have been preserved for over a hundred years. The exhibition is built on a diorama principle, representing the characteristic landscapes of the area and its natural zones.

The ancient history of the region is reflected in the collection of animal bones from the Quaternary period. The dioramas display a mammoth skeleton, a woolly rhinoceros skull, and other remains. The geological history is represented by samples of sedimentary rocks and a paleontological collection.

The nature department hosts temporary exhibitions, such as a private collection by V. Ulanov dedicated to antique items for preparing and serving tea and coffee. Each exhibit has its own story, including bulotki, which were used as samovars in Europe and Russia.