Clarifying the relationship between ecosystem services (ESs) and human well-being (HWB) is crucial for ensuring ecological security and guiding sustainable development in China’s ecologically prioritized but economically underdeveloped regions. However, the ability of ESs improvements to effectively enhance HWB remains uncertain amid the twin challenges of environmental conservation and poverty alleviation. This study assessed the spatiotemporal coordination between ESs and HWB across functional zones in the GTAP region from 2000 to 2020, using a Sustainable Development Goal (SDG)-oriented framework. Results showed that all five ESs improved to varying degrees, with the greatest increases in agricultural areas. HWB increased most rapidly in agricultural zones, rising by 133.1%. The agro-pastoral ecotone exhibited moderate ESs improvement and relatively stable HWB, while pastoral areas, despite limited ESs increases, achieved HWB levels comparable to agro-pastoral ecotone by 2020. Despite these improvements, the overall coupling coordination between ESs and HWB remained low, with habitat quality (HQ) showing the highest correlation (0.4–0.5) and soil retention (SR) the lowest (0.1–0.2). Spatial coordination improved most in pastoral areas, where equilibrium areas expanded by 350.5%. Mechanism analysis revealed significant spatial heterogeneity: stable provisioning services were the main driver of HWB improvement in agricultural areas, while their instability constrained progress in pastoral areas. In the agro-pastoral ecotone, enhanced supporting services played a key role in sustaining HWB. These findings emphasize the importance of both enhancing and stabilizing ESs delivery to promote sustainable, equitable HWB, providing a foundation for targeted socio-ecological management strategies in fragile regions.