The exchange of carbon dioxide is a key measure of ecosystem metabolism and a critical intersection between the terrestrial biosphere and the Earth's climate. Despite the general agreement that the terrestrial ecosystems in North America provide a sizeable carbon sink, the size and distribution of the sink remain uncertain. We use a data-driven approach to upscale eddy covariance flux observations from towers to the continental scale by integrating flux observations, meteorology, stand age, aboveground biomass, and a proxy for canopy nitrogen concentrations from AmeriFlux and Fluxnet-Canada Research Network as well as a variety of satellite data streams from the MODIS sensors. We then use the resulting gridded flux estimates from March 2000 to December 2012 to assess the magnitude, distribution, and interannual variability of carbon fluxes for the U.S. and Canada. The mean annual gross primary productivity (GPP), ecosystem respiration (ER), and net ecosystem productivity (NEP) of the U.S. over the period 2001–2012 were 6.84, 5.31, and 1.10PgCyr−1, respectively; the mean annual GPP, ER, and NEP of Canada over the same 12-year period were 3.91, 3.26, and 0.60PgCyr−1, respectively. The mean nationwide annual NEP of natural ecosystems over the period 2001–2012 was 0.53PgCyr−1 for the U.S. and 0.49PgCyr−1 for the conterminous U.S. Our estimate of the carbon sink for the conterminous U.S. was almost identical with the estimate of the First State of the Carbon Cycle Report (SOCCR). The carbon fluxes exhibited relatively large interannual variability over the study period. The main sources of the interannual variability in carbon fluxes included drought and disturbance. The annual GPP and NEP were strongly related to annual evapotranspiration (ET) for both the U.S. and Canada, showing that the carbon and water cycles were closely coupled. Our gridded flux estimates provided an independent, alternative perspective on ecosystem carbon exchange over North America.