The Danube Delta is Europe's largest wetland system and of unique biogeographical character. Whilst its geomorphological evolution is relatively well-known its ecological history is poorly understood, including the history of human impact, as a result of the dynamic nature of deltaic systems, and the scarcity of reliably dated successions. In this paper, we report a multi-proxy record of palynology, sediment texture, geochemistry, and ostracods from the upper reaches of the Danube Delta. We use these data to reconstruct a mid-to-late Holocene history of vegetation and environmental changes at local and regional scales, which serve as a model for understanding baseline conditions in delta apex regions. From 7500 to 6200 cal yr BP, the study site was part of an inter-distributary channel-levee system connected to coastal lagoons and sensitive to sea-level fluctuations but transitioned to a partially-disconnected lacustrine environment after 5700 cal yr BP. These geomorphologically-driven landscape changes strongly influenced the pollen source area making it complex to interpret palynoassemblages. Prior to 5700 cal yr BP, palynoassemblages were predominantly river-transported, reflecting widespread hinterlands, and providing information for the regional reconstruction of the vegetation history in the northern Dobrogea region. These data reveal the early presence of Carpinus and Fagus in southeastern Romania, prior to their spread through the Carpathian Basin. After 5700 cal yr BP, initiated by a slowdown in the relative rate of rise of the Black Sea, peat accumulation commenced within the shallow lake depocentre and airborne pollen became the dominant source. These pollen data record an expansion of herbaceous taxa and highly diverse marsh and aquatic taxa. Tree cover became dominated by Quercus, with low percentages of Carpinus, Betula, Ulmus, and Tilia. The earliest pollen evidence indicative of human impact commences c. 6500 cal yr BP) and, after 3200 cal yr BP, the decline in Quercus and a synchronous rise in archaeological artifacts, points to an opening of the landscape by forest clearance and an enlargement of arable areas. In particular, clearance and agriculture during the development of the Hallstattian Babadag culture (c. 3200-2800 yr BP) reflects an increase in population and settlement density during that late interval. Our paper comprises the first mid-to-late Holocene palynological record for the Danube Delta and highlights how human activity has profoundly altered the dryland region, creating landscapes comparable to today from around 3200 years BP, while the local deltaic landscape retained its character over the last six millennia.