Historical and future trends in net primary productivity (NPP) and its sensitivity to global change are largely unknown because of the lack of long-term, high-resolution data. Here we test whether annually resolved tree-ring stable carbon (δ13C) and oxygen (δ18O) isotopes can be used as proxies for reconstructing past NPP. Stable isotope chronologies from four sites within three distinct hydroclimatic environments in the eastern United States (US) were compared in time and space against satellite-derived NPP products, including the long-term Global Inventory Modeling and Mapping Studies (GIMMS3g) NPP (1982-2011), the newest high-resolution Landsat NPP (1986-2015), and the Moderate Resolution Imaging Spectroradiometer (MODIS, 2001-2015) NPP. We show that tree-ring isotopes, in particular δ18O, correlate strongly with satellite NPP estimates at both local and large geographical scales in the eastern US. These findings represent an important breakthrough for estimating interannual variability and long-term changes in terrestrial productivity at the biome scale.