Tradition of antique collection in Sisak has existed for more than 150 years, but the museum as an institution was established only in 1951. At the initiative of engineer Jerko Bauer, company "Museum and Library of the City of Sisak" was founded with the purpose of "collecting historical and art objects and arranging museum collections and library". On the occasion of the constituent assembly, core objects of the museum collection were exhibited.

After the World War II, in 1945, the company reported its existence to the National Authorities and continued to operate under the name "City Museum of Sisak".

The operation of the City Museum was included in the City Budget in 1951 and was allocated premises in the house of Katarina Colussi, today's Trg hrvatskih branitelja (Croatian Defenders' Square), and a first museum exhibition was opened on 1st May in the same year. Memorial Locksmith's Trade Exhibition", in which Josip Broz Tito (the then President of FNR Yugoslavia) was trained for the trade, was organized the same year in the Kralja Tomislava Street no. 10, and it was added to the City Museum.

Museum and Archive of the National Revolution was founded in Sisak in 1957, with the purpose of collecting and processing museum and archive materials related to "revolutionary workers' movement, National Defence War and Socialist Development in the area of Sisak, Petrinja, Glina, Kostajnica and Dvor". The museum bought a building in the Kralja Tomislava street no. 10 was bought for its needs of this museum and after that acquired authority over the "Memorial Locksmith's Trade Exhibition".

Based on decisions of the Assembly of Sisak Municipality dated 15th December 1964, City Museum and Museum and Archive of the National Revolution merged into one institution called Museum of Sisak. This institution has operated as an integrated organization since 1st January 1965 and performs its functions in the municipalities of Sisak, Petrinja, Glina, Kostajnica and Dvor. The Museum opened a department for protection of cultural works on 22nd December 1967. It covers the above-mentioned municipalities and the areas of municipalities of Kutina, Ivanic Grad and Novska.

Instead of the "Calussi" building (today a building of the County Land Cadastre), in 1966, the Municipal Assembly of Sisak allocated a building on the Ban Jelacic Square no. 6 - Big Capitol, a cultural monument of I. category, and after its reconstruction in 1968, the fortress of Old town of Sisak, a monument of the 0 Category.

In accordance with such developments and spatial expansion, Museum of Sisak has developed into a complex homeland museum with the following collections: archaeological with numismatics, ethnographic, cultural-historical, gallery, collection of workers' movement and collection of National Defence War and Socialist Development and accompanying departments: preparatory workshop, professional library, photo workshop and photo laboratory.

In 1980, the Museum organized activities on preparation and publishing of edition, which dealt with "… progressive workers' movement of the national defense war and socialist revolution in the area of the town of Sisak".

In line with social and political changes in 1990, activities on this edition were stopped and the already collected archive materials were compiled with the rest of the museum collections: workers' movement, national defense war and socialist development, which together form a collection of the latest history and contemporary times.

The new Statute and Manual on internal organization and activities of the Museum changed its title into City Museum of Sisak in 1995, which established its new scope of activity.

In the course of the last fifty years, more than 25,000 of items were collected and prepared by professionals, through research, acquisition, and donations or as gifts.

The Museum actively participated in the cultural and educational life of the town by organizing permanent and occasional museum and gallery exhibitions accompanied by posters, catalogues and brochures, appropriate lectures, scientific gatherings and as a publisher or co-publisher of several anthologies, monographs and calendars.