The abundance and spatial distribution of mercury in soil samples covering nearly the whole of China (c. 9 million km2) were obtained by the China Geochemical Baseline (CGB) project from 2008 to 2015. From the data and maps, it was found that the Hg contents both in the top (0–25 cm) and deep soil (below 100 cm or C-horizon) of the karst area in southwestern China are richer than that of any other geographical landscape areas. Median Hg values for this karst area are 113 and 90 µg/kg respectively (n = 126), in the top and bottom soils, much higher than the corresponding data of 26 and 18 µg/kg for the entire country (n = 3380). This regional-scale high Hg distribution is due mainly to high Hg geochemical backgrounds in bedrock and soil formation on limestone. A large-scale epithermal metallogenic domain developed in southwestern China and the extensive distribution of Lower Cambrian black shale in southwest China led to a high Hg geochemical background for parent rocks of soils. The chemical weathering of carbonate minerals and the geochemical behaviour of Hg in the epigenetic environment result in Hg enrichment by ferric oxides, iron hydroxide and organic carbon in limestone soils. Human activities mostly result in local-scale Hg anomalies, but have little effect on this regional-scale anomaly.