Abstract Since 2000, vast areas of cropland in the rural mountain areas of China have been abandoned for reasons including labor loss and rapid urbanization, although the spatiotemporal patterns and causes of abandoned cropland (ACL) are not fully understood. We investigated changes in cropland abandonment in the Guizhou–Guangxi karst mountain area (GGKMA). We used the Moderate Resolution Imaging Spectroradiometer normalized difference vegetation index in conjunction with phenology metrics to obtain the land-use trajectory from 2001 to 2015, and then mapped the extent of cropland abandonment based on this land-use trajectory and local crop rotation cycle. We found that 10.45% (2.24 × 104 km2) of cropland in the GGKMA has been abandoned since 2001. In three sub-periods (2001–2005, 2005–2010, and 2011–2015), the overall trend showed an initial increase and then a slight decrease in the cropland abandonment rate (CAR) of 11.55%, 19.29%, and 17.17%, respectively. We explored the effects of environmental and socioeconomic factors on differences in the CAR by applying a multi-level model approach. About 26% and 16% of the variances in CAR were explained at the county and small watershed levels. At the small watershed level, spatiotemporal changes in CAR were primarily influenced by farming and soil conditions, while the severity of soil hydraulic erosion was a key factor in determining the distribution of CAR. Rural depopulation, the decline of agricultural activity, and low levels of education had significant positive effects on the increasing CAR, while the “feminization” of agriculture had the opposite effect on CAR at the county level. The results of this study implied that the spatial variation of abandonment may be influenced by environmental constraints, while socio-economic changes were the direct cause of the temporal trend of abandonment. Government should encourage farmers to increase the vegetation cover rather than continually undertake unsustainable agricultural activities in the areas with steep slopes and eroded soil, as well as strive to reduce the production costs associated with scattered plots, poor agricultural infrastructure, and the rising opportunity cost of labor. This could include conducting land consolidation and transfer, and providing agricultural subsidies.