For almost two decades, the relationship between prehistoric natural disasters that struck the Guanting Basin in northeast Tibetan Plateau and the destruction of Lajia, an archeological site, has attracted scholarly attention and been widely discussed. Whereas most studies have focused on the impacts of disasters on a single site within the Guanting Basin, few have examined patterns of spatiotemporal evolution of human settlements from the Neolithic to the Bronze Age. Consequently, there is a lack of clarity on the processes and mechanisms underlying the evolution of prehistoric human-land relationships in the Guanting Basin. We therefore examined spatiotemporal variations in settlements in the Guanting Basin during the period, based on the locations, altitudes, and areas of archaeological sites. We found that four sites were located on the third terrace of the Yellow River during the late Yangshao period (5500–5000 cal yr BP) and distributed within a small area. During the period between the Majiayao and Qijia cultures (5300–3600 cal yr BP), the number of sites evidently increased and the scale and distribution of settlements expanded, with settlements generally shifting toward the lower elevation areas of the Guanting Basin. During the Xindian period (3400–2700 cal yr BP), the number and scale of sites showed a downward trend and the distribution of settlements contracted. The Xindian settlement underwent altitude-based spatial differentiation, with some groups moving to areas at higher altitudes and others remained in lower altitude areas. Moreover, we found that the number, scale, and distribution range of Neolithic and Bronze Age sites in the Guanting Basin were closely related to the evolution and distribution patterns of prehistoric cultures in the regions of Gansu and Qinghai, which were further affected by climate change and agricultural development. Furthermore, there is no evidence that the altitudinal distribution pattern of Neolithic and Bronze Age settlements in the Guanting Basin was influenced by paleofloods rather it was primarily influenced by changes in subsistence strategies.