In April 1919, the district commission initiated the creation of a museum in Kasimov. In July, a museum sub-department was organized under the District Department of Education, which became the Kasimov Local History Museum in 1921. The museum's establishment involved A. A. Mansurov, I. A. Kitanitsev, S. K. Bulatova, V. I. Kislov, A. A. Olenin, and others, many of whom were members of the Society of Researchers of the Ryazan Region. Museum staff actively engaged in collection, education, and research work. During this period, the foundation of the museum collection was laid, with significant credit going to the first director of the museum, Ivan Alexandrovich Kitanitsev.

Initially, the museum's collections were formed from valuables received from the estates of the Golitsyn and Olenin princes, as well as from closed churches and monasteries. However, in 1928, after the arrest of director I. A. Kitanitsev, the museum lost its premises, and its funds were moved to the warehouses of the District Department of Education.

In 1939, the museum was given the building of the former Khan Mosque, and it was then decided to create two departments in the museum: natural history and history. The Kasimov Local History Museum was located in this monument of Tatar architecture for a long time, which now serves as the storage facility for the museum-reserve. The Great Patriotic War brought changes to the museum's life, creating the need for the evacuation of exhibits. However, the hostilities bypassed Kasimov, and urgent evacuation was not required. In 1998, the museum was allocated another building, a mansion of the Alyanchikov merchants from the 19th century. Gradually, local history materials began to dominate the museum's collection, and in 2002, a permanent exhibition titled 'History of the Kasimov Region from Ancient Times' was created. On November 19, 2015, the museum was renamed the 'Kasimov Historical and Cultural Museum-Reserve,' marking an important step in its development as a historical, cultural, and tourist center of the region. Prior to this, there was no museum-reserve in a small historical town in the Ryazan region, and with the emergence of the Kasimov museum-reserve, the situation changed. Kasimov is unique in that its cultural objects are located outdoors, and the architectural appearance of the city maintains its integrity and pristine nature.

The museum-reserve includes architectural monuments of Cathedral Square, the territory of the Kasimov Kremlin, 19th-century estate complexes, as well as civil and religious buildings.

Today, the museum's collection consists of over 42,000 storage units, which are constantly replenished with items reflecting the modern history of the region. The Kasimov museum-reserve possesses collections of visual arts, wooden polychrome sculptures from the 17th-18th centuries, and artistic castings from the Batashev factories. The exhibition features Kasimov hand bells and clay Vyrkov toys.

The ethnographic department of the museum showcases traditional peasant costumes of the Kasimov district, as well as outfits, headgear, and jewelry of the Kasimov Tatars. A special place in the collections is occupied by memorial items from the noble families of Golitsyn and Olenin, furniture, works of visual art, and a rich collection of written sources, including manuscripts, musical notebooks, and a scientific library.