Paleoclimate change and anthropogenic activities have fundamentally modified the Earth's environmental system since the late Quaternary. Southwest China has one of the largest continuous karst areas in the world, yielding geological records from karst depressions that can improve our understanding of changes in the dominant control on regional environmental conditions. In this study, we investigated a sediment sequence formed over 33,000 years in a typical karst catchment by using combined geophysical, geochemical and biological properties of the depression deposits. The results suggest that paleoclimate change was the main modulator of environmental changes prior to the Late Holocene, and that significant vegetation change related to paleotemperature influences played an important role during the Early (ca. 12–8 ka) and Middle (ca. 8–4 ka) Holocene. During the Late Holocene (ca. 4–0 ka), the impact of anthropogenic activities has overwhelmed paleoclimatic influences on the environment. This study demonstrates the utility of dated karst depression deposits for reconstructing Holocene climate change and the timing of anthropogenic impacts on the landscape.