The urgent need to maintain ecosystem provisioning services and achieve urban sustainable development goals has led to a long-standing focus on the driving effects of land urbanization (LU) in the Middle Reaches of the Yangtze River Urban Agglomeration (MRYRU) on vegetation cover system productivity. Previous studies have lacked consideration for the long-term correlation between land urbanization (LU) and the Gross Primary Productivity (GPP) of vegetation, as well as the spatial non-stationarity of LU’s impact in the region. This study is based on land cover remote sensing data and GPP imagery data to monitor the long-term evolution trends of LU and GPP in MRYRU from the perspectives of townships and grids. It further investigates the spatial correlation and clustering characteristics between the two using bivariate spatial autocorrelation method. Additionally, a Geographically and Temporally Weighted Regression (GTWR) model was employed to analyze the spatial effects of LU on GPP. The results indicate that the GPP of MRYRU grows to 1572.88gCm-2a-1 with an average annual growth rate of 0.848% from 2000 to 2020. High-value areas are distributed in the central and eastern mountainous of the urban agglomeration, while low-value areas gradually formed an “n”-shaped clustered distribution pattern. The negative spatial autocorrelation between LU and GPP shows a general upward trend, and Low-High is the dominant agglomeration type, concentrated in Hengyang and some mountainous cities in Jiangxi Province. The overall negative impact of land urbanization on GPP in MRYRU is maintained in the spatially nonstationary pattern of driving coefficients, with negative impact areas mostly concentrated in the city’s main city zone and positive impact areas concentrated in the urban agglomeration’s mountainous townships. This study provides support for MRYRU to adopt more resilient land optimization management strategies and vegetation ecological restoration plans.