A paleoenvironmental reconstruction of the landscape of Nea Raedestos Toumba in the Anthemous River valley in central Macedonia, Greece is undertaken using multidisciplinary geoarchaeological methods. The archaeological site is a settlement mound (tell or toumba) that dates to the Neolithic period and the Bronze Age. The tell’s location on the alluvial plain prompted a multidisciplinary investigation to reconstruct the influence of landscape changes on prehistoric settlements in the valley with an emphasis on alluvial sequences. An electrical resistivity tomography survey and three cores were drilled to study the sedimentary environments in and around the archaeological site. Sedimentologic and palynological analysis combined with accelerator mass spectrometry radiocarbon dating show that the oldest habitation layers at the site, from the Middle and Late Neolithic, were located next to a small, periodically drying water body surrounded by ruderal vegetation. Diatom analysis suggests that this water body was supplied by saline/brackish groundwater. The water body was open until the Early Bronze Age, when it was filled and buried by floodplain sediments. This flooding phase at Nea Raedestos likely occurred at the same time as an increase in fluvial aggradation in the neighboring Thessaloniki Plain, which is dated to the beginning of the third millennium BC.