Prijepolje Museum was opened in 1990 with a complex museum collection. In 1995, it was granted the status of a regional museum covering the territories of the municipalities of Prijepolje and Priboj.

For 30 years the Prijepolje Museum has conducted major projects for the reconstruction of demolished medieval monasteries, reconstruction and protection of Islamic monuments, scientific research and reconnaissance of terrains, scientific meetings, lectures, museum exhibitions in the country and abroad and major visual arts projects. The project of reconstruction and extension of the museum building (2005-2007) with the National Investment Plan funds was designated a project of priority in the culture of Serbia.

On 19 May 2012 in Portugal, in the competition of 59 European museums, the European Museum Forum under the auspices of the Council of Europe awarded the Museum in Prijepolje the special commendation for developing authorial national projects funded by the Ministry of Culture of the Republic of Serbia for the positive social influence in the complex and delicate multi-ethnic environment, working strategically to present and preserve the cultural heritage and succeeding in establishing cooperation with national museums in the region, paving the way for cooperation despite the unfavourable political situation. This commendation is the first such recognition ever to be awarded not only in Serbia, but in the wider region of this part of Europe. The award is a great recognition, not only for the Prijepolje Museum, but for Serbian museology in general.