Net primary productivity (NPP) is highly sensitive to multiple stressors under progressive and intensifying climate change and anthropogenic impacts. The importance of understanding spatiotemporal distribution patterns and the associated driving factors that govern estuary NPP is paramount for regional carbon (C) budget assessments. Using a combined remote sensing and machine learning (ML) approach, the average NPP of the Yangtze Estuarine−offshore continuum (YEOC) was measured at 273.19 ± 21.26 mgC m −2 day −1 over the past two decades. Temporally, NPP exhibited a significant downward trend between 2002 and 2022. Climate factors (climate fluctuations, sea level rise, and discharge) drove phytoplankton biomass (Chl-a) while light conditions (PAR and K d490 ) affected photosynthesis rates. Together, they can explain 65% of the NPP variation. Anthropogenic disturbances (i.e., damming and nutrient emissions) were not significant. Additionally, changes in NPP decreased phytoplankton C sequestration rates from 11.9 to 10.4 Tg C year −1 , reducing the estuary's C sink capacity, which relies on biological C fixation. This study highlights the climate's influence on the spatiotemporal transformation of YEOC NPP while enhancing our understanding of the response of EOC C budgets to climate change and anthropogenic activities.