China’s Grain to Green Program (GTGP), which is one of the largest payments for ecosystem services (PES) in the world, has made significant ecological improvements to the environment. However, current understanding of its outcomes on the social-ecological system (SES) remains limited. Therefore, taking the South China Karst as an example, a SES resilience evaluation index system was constructed followed by an exploratory spatial analysis, root mean square error, and Self-Organizing Feature Map to clarify the spatiotemporal changes and relationship of SES resilience, achieve the zoning of SES resilience and provide restoration measures. The results showed an upward trend in social resilience from 2000 to 2020, especially its subsystem of social development. Regional ecological resilience was stable, owing to a slightly declined ecosystem services and increased landscape pattern. Spatially, nearly half of the counties exhibited a distribution mismatch in SES resilience. There was an obvious inverted U-shaped relationship of SES resilience, indicating a clear threshold effect, and the constraint relationship of SES resilience eased over time, demonstrating the effectiveness of the ecological restoration program. GTGP played a positive role in reducing regional SES trade-off, but this positive effect was limited, reflecting the limitations of overemphasizing the conversion from farmland to forest and grassland. Regional SES resilience can be divided into four clusters, which were the key optimization zone for social system, the SES resilience safety zone, the key restoration zone for SES resilience, and the key optimization zone for ecological system. Adaptive adjustments for the GTGP in these zones should be taken to achieve maximum SES benefits in the future.