The origins of the Panevėžys Museum can be traced back to the beginning of the 20th century. Even at that time, attempts were made to combine the collections from the private collections into a single exhibition. The city Duma considered the establishment of a museum and library in 1908. The municipality understood the importance of these institutions, but their establishment was delayed due to lack of funds.

With the establishment of the modern state of Lithuania, the research of the homeland rose to a completely different level. A group of enthusiasts started collecting ethnographic material at Panevėžys Men’s Gymnasium as early as 1919. A group for the study of the Homeland, the first regional ethnographic society in Lithuania, was established there in 1923. The following year, the Society for the Study of the Panevėžys Homeland was established, one of the main tasks of which was the establishment of a museum. The initiators of the establishment of the society and museum are the county governor Vladas Rozmanas (who later contributed a lot to the establishment of the museums of Rokiškis and Biržai), the famous naturalist Jurgis Elisonas, linguist and teacher Petras Būtėnas, teacher Petras Bliumas, lawyer and public figure Jonas Moigis. Thanks to these people the first exposition of the museum was solemnly opened on 18 January 1925 in the oldest building of the city, the former archive of Upytė County Court, to commemorate the second anniversary of the annexation of Klaipėda region.