Following palaeobotanical, sedimentological and archaeological research recently conducted on and around the tell of Dikili Tash (Eastern Macedonia, Greece), we present continuous palaeoenvironmental data on this multi-period site. This study combines pollen, non-pollen palynomorphs (NPPs), macro-charcoal and sedimentological analyses that are compared with archaeological data from the Middle Neolithic to Antiquity period. It provides an overview of the local environment near the former Tenaghi-Philippon marsh and a comprehensive view of human impact on vegetation cover in lowlands. As early as ca. 4550 cal BC, an initial phase of change in vegetation cover, has been recorded. This period, in the Eastern Mediterranean region, is one of intensifying human activities and social interactions into the Balkan region, which resulting in the foundation and transformation of early Late Neolithic societies. Although the palynological record does not show the crops species grown, the intensive clearance resulted in the increase of open herbaceous landscapes with anthropogenic indicators. This, as well as the increase of macro-charcoal values strongly supports a more or less continuously shaping of the landscape by human induced fires. New tree species that also became established at this time include Olea and Castanea.. The presence of three main formations can be argued from the Early Neolithic to Antiquity: (1) riparian vegetation, (2) oak woodlands and (3) open vegetation in the form of wooded grasslands. Beyond the responses to climate changes, the vegetation composition reflects a regionally diversified land management system as indicated by a greater diversity in cultivated or harvested plants. The study reveals two phases of decline in land use directly on the edge of the marsh, although indicators of anthropogenic disturbance of the vegetation never entirely disappear during these periods between 3900-3300 cal BC at the transition from the Late Neolithic (LNII) to the Bronze Age and from 1650-800 cal BC when we observe a reorganization of the settlement on the higher slopes. In contrast, four periods are characterized by an increase in land use extension and intensification: Late Neolithic (4500-3900 cal BC); Early to Middle Bronze Age (3000-1600 cal BC), the Iron Age (1000-800 cal BC) and Antiquity during the Macedonian (ca. 357-148 cal BC) and Roman periods (148 cal BC – cal AD 395).