A major assemblage of Mesolithic and Neolithic wooden artefacts has been recovered from the bed of the River Užava at Sise, in the coastal belt of western Latvia. New archaeological investigation has also produced wooden remains and other evidence of occupation on the riverbank. On the basis of multi-proxy environmental data and radiocarbon dating, this article offers a first attempt to place the human activity in a palaeolandscape context. The earliest evidence of human presence is provided by wooden artefacts dated to c. 10,500–9700 cal. BP, during the Ancylus Lake transgression. These remains are thought to reflect fishing activities in the shallows of the Ventspils Bay, which existed during the transgression. The regression that followed brought a return to river-valley conditions at the site, and the next recorded period of human activity, evidenced by ¹⁴C-dated antler tool finds, is associated with the beginning of the Littorina Sea transgression, culminating c. 7500 cal. BP. With the formation of a new Ventspils Bay/Lagoon, the Sise site, at or near the river mouth, would have regained its status as an advantageous fishing location. Archaeological finds indicate continued human activity c. 6000–4000 cal. BP, even though the sea level was now lower and this was no longer a river-mouth location. Such a pattern of recurrent human occupation during the early to middle Holocene, associated with repeated shifts of the shoreline, appears to be characteristic of the central region of the Baltic Sea Basin.