Large urban areas are vulnerable to various geological hazards and anthropogenic activities that affect ground stability—a key factor in structural performance, such as buildings and infrastructure, in an inherently expanding context. Time series data from synthetic aperture radar (SAR) satellites make it possible to identify small rates of motion over large areas of the Earth’s surface with high spatial resolution, which is key to detecting high-deformation areas. Santiago de Chile’s metropolitan region comprises a large Andean foothills basin in one of the most seismically active subduction zones worldwide. The Santiago basin and its surroundings are prone to megathrust and shallow crustal earthquakes, landslides, and constant anthropogenic effects, such as the overexploitation of groundwater and land use modification, all of which constantly affect the ground stability. Here, we recorded ground deformations in the Santiago basin using a multi-temporal differential interferometric synthetic aperture radar (DInSAR) from Sentinel 1, obtaining high-resolution ground motion rates between 2018 and 2021. GNSS stations show a constant regional uplift in the metropolitan area (~10 mm/year); meanwhile, DInSAR allows for the identification of areas with anomalous local subsistence (rates < −15 mm/year) and mountain sectors with landslides with unprecedented detail. Ground deformation patterns vary depending on factors such as soil type, basin geometry, and soil/soil heterogeneities. Thus, the areas with high subsidence rates are concentrated in sectors with fine sedimentary cover and a depressing shallow water table as well as in cropping areas with excess water withdrawal. There is no evidence of detectable movement on the San Ramon Fault (the major quaternary fault in the metropolitan area) over the observational period. Our results highlight the mechanical control of the sediment characteristics of the basin and the impact of anthropogenic processes on ground stability. These results are essential to assess the stability of the Santiago basin and contribute to future infrastructure development and hazard management in highly populated areas.