The paper investigates potentials and challenges during the interpretation of prehistoric settlement dynamics based on large archaeological datasets. Exemplarily, this is carried out using a database of 1365 Neolithic sites in the Weiße Elster river catchment in Central Germany located between the southernmost part of the Northern German Plain and the Central Uplands. The recorded sites are systematically pre-processed with regard to their chronology, functional interpretation and spatial delineation. The quality of the dataset is reviewed by analyzing site distributions with respect to field surveys and modern land use. The Random Forests machine learning algorithm is used to examine the impact of terrain covariates on the depth of sites and pottery preservation. Neolithic settlement dynamics are studied using Site Exploitation Territories, and site frequencies per century are used to compare the intensity of land use with adjacent landscapes. The results show that the main trends of the Neolithic settlement dynamics can be derived from the dataset. However, Random Forests analyses indicate poor pottery preservation in the Central Uplands and a superimposition of Neolithic sites in the southernmost part of the Northern German Plain. Throughout the Neolithic the margins between soils on loess and the Weiße Elster floodplain were continuously settled, whereas only Early and Late Neolithic land use also extended into the Central Uplands. These settlement patterns are reflected in the results of the Site Exploitation Territories analyses and explained with environmental economic factors. Similar with adjacent landscapes the Middle Neolithic site frequency is lower compared to earlier and later periods.