Information on soil aggregate stability (SAS) is essential for assessing ecosystem services and scaling up soil erosion models. The global contributions of environmental factors (e.g., soil properties, topography, and climate) on SAS at a specific spatial scale are extensively documented. However, the scale- and location-specific controls of these factors are poorly understood. Here, using 2,238 topsoil (0-0.2 m) samples and 24 environmental factors, we quantified SAS variability across different spatial scales and locations in a karst region (43,700 km2) of southwestern China. We found SAS varied mainly at large scale (20 km) followed by medium scale (10 km) and small scale (2 km). Topographic variables, namely, slope, elevation, and plan curvature were key determinants of controlling SAS variability at small scale. Soil organic matter and precipitation were critical drivers affecting SAS variability at medium scale. Precipitation and cation exchange capacity were main factors controlling SAS variability at large scale. Specifically, slope primarily exhibited a negative influence on small-scale SAS variability in the southern region, and a positive effect in the northern region. At medium scale, soil organic matter generally exerted positive effects on SAS. At large scale, the primary influence of precipitation typically differs between the northernmost part and remaining region of the study area. These results reveal the scale- and location-specific controls of environmental factors on SAS that should be considered for digital soil mapping and designing region-based soil management.