Escalating global human activities elicit diverse ecosystem service responses, yet understanding remains limited. This study establishes a framework to clarify these responses, focusing on the Yangtze River Economic Belt in China. Analyzing 2000–2020 data, it calculates ecosystem service economic value and human footprint index. It introduces the ecosystem services response index and comprehensive responsiveness index to assess response characteristics and intensity to anthropogenic pressures. Results show a fluctuating decline in ecosystem services and an increase in anthropogenic pressures. There is a nonlinear relationship: ecosystem services decline with rising pressures, following a U-shaped trend. Notably, nonurban agglomerations experience more significant ecosystem service evolution than urban agglomerations due to differing environmental conditions. This highlights regional disparities in human activity impacts on ecosystems, crucial for planning.