The museum is located on three plots of land on Didžiojo Vandens Street, along the former Dangė old riverbed, where the river flowed until the mid-17th century. In the first half of the 16th century, buildings appeared to the south of the Dangė old riverbed, and in 1540, 16 fishing families settled there. Later, this area, which belonged to the castle, was used to accommodate the castle soldiers and working staff,  curriers settled down along the Dangė. As a result, the suburb came to be known as Odų Street. In 1589 46 families lived there. In the first half of the 17th century, the town was surrounded by a system of bastion fortifications, and the suburb of Odų Street, along with the Old Town, was included. In the mid-17th century, the Old Town was completely overbuilt. Therefore, in 1667, the Dangė old riverbed and the bodies of water in the suburb began to be filled in. After the filling of the old riverbed, Didžioji Vandens Street and the plots alongside it were developed. The suburb became an integral part of the town and in 1692 was given the name of Friedrich’s suburb. In 1722 the suburb was adjoined to the town.

In the 18th and 19th centuries on Didžioji Vandens Street—inns, bakeries, breweries, shops, various workshops settled—it was one of the busiest and most painting like streets of the former suburb. Building at 2 Didžioji Vandens Street is one of the oldest residential buildings in Klaipėda. It was built in 1773-1774 by the postmaster J. Ch. Witte. The house at 2 Didžioji Vandens Street is a Baroque building. As the Baroque did not have the right economic conditions to spread in Klaipėda (poorly developed trade, no wealthy merchant class), it lasted for a short time, only in the second half of the 18th century, and compared to other cities was modest. In buildings there are few panel elements, sculptures, elaborate masonry pediments (in the second half of the 18th century there were no professional sculptors and modelers in Klaipėda). Klaipėda Baroque, as well as the museum building, is characterised by mansard roofs and moderate architectural details. In the 19th and first half of the 20th centuries, the building belonged to craftsmen and small merchants.

The building at 8 Didžioji Vandens Street was built at the end of the 18th century. During the archaeological investigations in the basement in 1980-1981 (archaeologist J. Genys), the earliest layers of the late 17th century were discovered, and it was found that the building had been reconstructed several times, in the second half of the 18th century it had acquired its present plan, in the first half of the 19th century the basement vaults were built with masonry. The land and buildings belonged to big merchants. The architecture of the building reflects that. Typically, merchants’ houses had semi-basements where goods were stored, and those goods were rented out to visiting merchants from other towns during fairs. As a result, the external staircase to the building was high, wooden until the mid-19th century, and then replaced by masonry one after a fire in 1854. The third plot was occupied by a blacksmith shop in the 19th and first half of the 20th centuries. The buildings were destroyed in the Second World War. In the 1980s, in this complex of buildings, it was decided to set up the city’s exposition of the Achievements of the National Economy. The building complex was renovated and a new building was constructed according to the project of architects N. and V. Zubov. On 5 November 1987, the exposition of the Achievements of the National Economy was opened, but it was open only for a short time. On 17 June 1988, the buildings were handed over to the History Museum of Lithuania Minor. At first it housed temporary expositions, but on 1 August 1992 the first permanent exposition halls for prehistory, numismatics and cartography were opened.