The Vietnamese Mekong delta is subsiding due to a combination of natural and human-induced causes. Over the past several decades, large-scale anthropogenic land-use changes have taken place as a result of increased agricultural production, population growth and urbanization in the delta. Land-use changes can alter the hydrological system or increase loading of the delta surface, amplifying natural subsidence processes or creating new anthropogenic subsidence. The relationships between land use histories and current rates of land subsidence have so far not been studied in the Mekong delta. We quantified InSAR-derived subsidence rates for the various land-use classes and past land-use changes using a new, optical remote sensing-based, 20-year time series of land use. Lowest mean subsidence rates were found for undeveloped land-use classes, like marshland and wetland forest (~6–7 mm yr−1), and highest rates for areas with mixed-crop agriculture and cities (~18–20 mm yr−1). We assessed the relationship strength between current land use, land-use history and subsidence by predicting subsidence rates during the measurement period solely based on land-use history. After initial training of all land-use sequences with InSAR-derived subsidence rates, the land-use-based approach predicted 65–92% of the spatially varying subsidence rates within the measurement error range of the InSAR observations (RMSE = 5.8 mm). As a result, the spatial patterns visible in the observed subsidence can largely be explained by land use. We discuss in detail the dominant land-use change pathways and their indirect, causal relationships with subsidence. Our spatially explicit evaluation of these pathways provides valuable insights for policymakers concerned with land-use planning in both subsiding and currently stable areas of the Mekong delta and similar systems.