The supply capacity and trade-off/synergy relationship of ecosystem services have been widely used in the study of ecological protection and ecological security zoning. However, existing studies may primarily focus on one aspect of the supply capacity or the trade-off/synergy relationship of ecosystem services, ignoring the nonlinear response of ecosystem service to driving forces during the zoning process. Here, taking southwest China as an example, we estimated the supply capacity and trade-off/synergy relationship of soil conservation, water production, net primary productivity and food supply, and constructed a supply index, a relationship index and a comprehensive index for ecosystem services. Further, we analyzed the spatiotemporal characteristics of the three indexes, explored the constraint relationship between the main driving forces and the comprehensive index, identified the critical thresholds, and clarified the regional ecological safety zoning and optimization plans. It was found that: (1) From 2000 to 2020, the supply index for ecosystem services slightly increased, reflecting the positive effect of ecological restoration; while there was obvious trade-off relationship of local regions in the maximizing pursuit of ecosystem service supply. It is necessary to incorporate both ecosystem service supply and trade-off/synergy relationship into the ecological safety zoning. (2) Spatially, the regions with low-value of the three indexes were highly overlapped and located in the western Sichuan Plateau, while the distribution of the regions with high value differed. The regions with high supply index were distributed in the southwest corner of the study area, and the regions with high relationship index and comprehensive index were concentrated in the east part. (3) Nature-society condition, vegetation-environment condition, and social-economy condition were main forces affecting the change of comprehensive index. There was an inverted U-shaped relationship between the driving forces and comprehensive index, indicating a clear threshold effect. The constraints of nature-society condition and vegetation-environment condition on the comprehensive index tightened over time. (4) The study area was dominated by the relative restoration area, followed by the relative safety area and key restoration area, and the absolute safety zone was with the smallest area. In the future, adjustments can be made to the constraint forces in different zoning to achieve the maximum supply and optimal relationship of regional ecosystem services.