The stressful effects of urbanization on vegetation net primary productivity (NPP) and vegetation–carbon cycle functions within the Yangtze River Economic Belt (YEB) under the sustainable development goals (SDG) and the concept of coordinated regional development, have garnered growing attention. Existing studies have been insufficient in comprehensively examining both the global effects and local variations resulting from urbanization in the region. Additionally, insufficient attention has been given to the heterogeneity of the ecological negative effects of urbanization in the three major urban agglomerations within the YEB. Based on multivariate remote sensing image and socioeconomic statistics data, this study integrates population, economic and land dimensions to construct comprehensive urbanization indexes and quantify the spatio-temporal evolution patterns of NPP and urbanization in the YEB. The focus is on detecting the global response of NPP to urbanization using the Spatial Durbin model and discussing the local heterogeneity of the effect in the Yangtze River Delta urban agglomeration (YRD), the middle reaches of Yangtze River urban agglomeration (MRYRU), and the Chengdu-Chongqing urban agglomeration (CCU) based on a geographically weighted regression model. The results show that the average NPP of the YEB increased from 592g*c/m2 to 670g*c/m2 at a rate of 0.621% from 2000 to 2020, with the most significant growth in the CCU, and the overall pattern of change is “increased in the north and decreased in the south”. The negative spatial autocorrelation between urbanization and NPP is becoming increasingly significant, and the negatively correlated clusters is the dominant type of local autocorrelation, among which the number of “High-Low” type cities is the largest and growing, mainly located in the northern regions of Anhui and Jiangsu. The significant negative effect of urbanization on the productive capacity of vegetation cover systems was verified, and a negative spillover effect that far exceeded the local negative effect was also confirmed. The effect of urbanization on NPP has significant local variability and gradually shifts to the effect pattern of positive effect in the east and negative effect in the west, while the pattern of urbanization-driven effects in the three urban agglomerations also continues to change. This study increases the concern about the negative ecological effects of urbanization, and more importantly, provides a basis for the joint action of ecological restoration and management in the Yangtze River Economic Belt and the implementation of differentiated governance policies around urban agglomerations.