Backgrounds A large-scale ecological restoration project was initiated in the 1990s in southwest China, which is one of the largest areas of rocky desertification globally. However, the influence and potential mechanisms of vegetation restoration on soil carbon(C) sequestration in karst and non-karst regions remains unclear. Methods Based on field investigation and multi-source data synthesis, the mechanisms of soil C sequestration were investigated to determine the most important variables affecting the rate of soil C change (Rs) in southwest China. Results Our results show significant differences in soil C sequestration between karst and non-karst regions with faster and longer C sequestration occurring in karst regions. In these areas, Rs was approximately 31% higher than in non-karst soils. The Rs of shrubland, grassland and cropland sites in karst areas was significantly higher than that observed in non-karst areas. We found that temperatures were the primary factor inhibiting soil C sequestration instead of precipitation. The total effect of nitrogen (N) on Rs was positive in both karst and non-karst regions. Conclusions Phosphorus was the dominant factor limiting the use of N by vegetation in karst regions and then resulting in limitation of C sequestration. The results indicated that soil C storage may increase intermittently due to combination of karst environment and climate change in southwest China in future.