The linear relationship between gross primary productivity (GPP) and evapotranspiration (ET), evidenced by site-scale observations, is well recognized as an indicator of the close interactions between carbon and hydrologic processes in terrestrial ecosystems. However, it is not clear whether this relationship holds at the catchment scale, and if so, what are the controlling factors of its slope and intercept. This study proposes and examines a generalized GPP-ET relationship at 380 near-natural catchments across various climatic and landscape conditions in the contiguous U.S., based on monthly remote sensing-based GPP data, vegetation phenology, and several hydrometeorological variables. We demonstrate the validity of this GPP-ET relationship at the catchment scale, with Pearson’s r ≥ 0.6 for 97% of the 380 catchments. Furthermore, we propose a regionalization strategy for estimating the slope and intercept of the generalized GPP-ET relationship at the catchment scale by linking the parameter values a priori with hydrometeorological data. We validate the monthly GPP predicted from the relationship and regionalized parameters against remote-sensing based GPP product, yielding Kling-Gupta Efficient (KGE) values ≥ 0.5 for 92% of the catchments. Finally, we verify the relationship and its parameter regionalization at 35 AmeriFlux sites with KGE ≥ 0.5 for 25 sites, demonstrating that the new relationship is transferable across the site, catchment, and regional scales. The relationship will be valuable for diagnosing coupled water–carbon simulations in land surface and Earth system models and constraining remote-sensing based estimation of monthly ET.