Archaeological, geological, and paleoecological investigations supported by radiocarbon dating enabled us to present a reconstruction of chronologically based paleoenvironmental and human activity changes in the Šventoji region, NW Lithuania, during the period 4000–800 cal BC. In addition, we describe the main stages of the Late Glacial and Holocene periods in the area. The Baltic Ice Lake regression was succeeded by a terrestrial period until the Littorina Sea maximal transgression at 5700–5400 cal BC. A marine bay with brackish water was transformed into a freshwater lagoon before the oldest archaeological evidence of human presence, i.e. 4000/3700 cal BC. However, the presence of Cerealia type and Plantago lanceolata pollen dating back to about 4400–4300 cal BC suggests earlier farming activities in the area. Pollen analyses show the minor but continuous role of cereal cultivation after 3250 cal BC. Due to the predominance of the boggy landscape in the immediate vicinity of the Šventoji sites, agricultural fields were situated further away from the sites themselves. Exploitation of remote areas of the freshwater basin by diverse fishing gear was proven by the discovery of a new fishing site, Šventoji 41 (2900–2600 cal BC). This finding together with data of previous research suggest a complex and elaborate coastal economy involving seal hunting and year-round freshwater fishing during the 3rd millennium cal BC. A decline in human activity is seen in the pollen diagram after 1800 cal BC, which could be due to significant environmental changes, including overgrowth of the freshwater lagoon basin with vegetation.