An understanding of soil moisture variability is necessary to characterize the linkages between a region's hydrology, ecology, and physiography. In subtropical karst region, the spatial variability of surface soil moisture is still unclear for the rocky ecological environment and intensive land uses. The purpose of this study was to characterize the variation and patterns of soil moisture content at depth of 0–16 cm and to investigate their influencing factors in a karst depression area of southwest China. Soil moisture content was measured at 20 m intervals by intensive sampling on March 11 (dry season) and August 30 (rainy season) in 2005, respectively. Surface soil moisture presented a moderate variability in the depression area at the sampling times. The variability was relatively higher in dry season with lower mean soil moisture, but lower in rainy season with higher mean soil moisture after heavy rain event. Similar results were also obtained from the mosaic patterns of soil moisture generated by ordinary Kriging interpolation with low standard deviations. This suggested that more soil samples might be required and the sampling interval should be shortened in dry season compared with rainy season. The dominant influencing factors on the variability of surface soil moisture were rainfall and land use types. However, altitude, bare-rock ratio, and soil organic carbon were also important factors, and exerted jointly to control and redistribute the surface soil moisture either in dry or rainy season in the depression area. Such information provided some insights for the study on eco-hydrological processes of vegetation restoration in the karst degraded ecosystem of southwest China.