The melting of the Scandinavian Ice-Sheet in the early Holocene allowed humans to populate the northernmost parts of Europe. Recent excavations of archaeological sites on the riverbank, floodplain and kame terraces of the River Rena, southeast Norway have defined periods of human occupation in riverside environments, which became ice-free during the last deglaciation. In this paper, we extend the scope of previous archaeological work by examining the sedimentology and chronology of five riverside sedimentary sequences along the River Rena. Our aims were to reconstruct the Holocene evolution of part of the river, and determine whether changes in Holocene settlement patterns might be linked to changes in river evolution and/or climate. Results show: (1) widespread draining of the kame terraces of the River Rena occurred shortly before the first consistent human settlement in the area began c. 8 ka BP; (2) human settlement was maintained until the present day, except during a period of previously undocumented abandonment between c. 4 and 3 ka BP, associated with a sustained period of high river discharge. We link the establishment of first undisputable settlement to reduced water levels as glaciers retreated upstream during a ‘warmer’ phase of the early Holocene, shortly after the 8.2 ka climatic downturn event. The most recent abandonment of the riverbank settlements 4—3 ka BP occurred during the last phase of glacier advance in the River Rena region, which has been linked to the Europe-wide late-Holocene Thermal Decline (Neoglacial) downturn in climate.