Karst ecosystems have become complex social-ecological systems (SESs) as a result of the interventions of large-scale ecological restoration programs, and the ecosystem services (ESs) that provide regional well-being can, to some extent, be described as social-ecological system services (S-ESs). Understanding the relationships among multiple S-ESs and exploring their drivers are essential for effective ecological management in karst areas, especially in regions differently affected by ecological engineering programs. Taking South China Karst (SCK) as a study area, we first identified two regions as comparative boundaries, namely significant engineering impact regions (SEERs) and non-significant ecological engineering impact regions (NEERs). Then we used ES assessment models, Spearman correlation, and optimal parameter geographic detector to identify the supply capacity, trade-offs/synergies, and their drivers of six types of S-ESs in SEERs and NEERs. The findings included: (1) SEERs were predominantly concentrated in the central and southern SCK regions, accounting for 33.98% of the total SCK area, with the most concentrated distribution observed in Guizhou and Guangxi. (2) Within the entire SCK, six S-ESs maintained a relatively stable spatial distribution pattern over time, with the most pronounced increase in soil conservation and a slight decrease in water retention, and the S-ES hotspots were more concentrated within the SEERs. (3) Most S-ES pairs within SEERs were optimized synergistically, with lower trade-off intensity and higher synergy intensity compared to NEERs. (4) S-ES pairs were affected by the interactions between the natural and socio-economic factors, with land use changes playing a crucial role, and natural factors were difficult to predict but cannot be ignored. Based on the results, we propose different SES sustainable development suggestions, with a view to providing theoretical support for the optimization of SES functions and the consolidating of integrated ecological construction.