We develop an approach for estimating net ecosystem exchange (NEE) using inventory-based information over North America (NA) for a recent 7-year period (ca. 2000–2006). The approach notably retains information on the spatial distribution of NEE, or the vertical exchange between land and atmosphere of all non-fossil fuel sources and sinks of CO2, while accounting for lateral transfers of forest and crop products as well as their eventual emissions. The total NEE estimate of a −327 ± 252 TgC yr−1 sink for NA was driven primarily by CO2 uptake in the Forest Lands sector (−248 TgC yr−1), largely in the Northwest and Southeast regions of the US, and in the Crop Lands sector (−297 TgC yr−1), predominantly in the Midwest US states. These sinks are counteracted by the carbon source estimated for the Other Lands sector (+218 TgC yr−1), where much of the forest and crop products are assumed to be returned to the atmosphere (through livestock and human consumption). The ecosystems of Mexico are estimated to be a small net source (+18 TgC yr−1) due to land use change between 1993 and 2002. We compare these inventory-based estimates with results from a suite of terrestrial biosphere and atmospheric inversion models, where the mean continental-scale NEE estimate for each ensemble is −511 TgC yr−1 and −931 TgC yr−1, respectively. In the modeling approaches, all sectors, including Other Lands, were generally estimated to be a carbon sink, driven in part by assumed CO2 fertilization and/or lack of consideration of carbon sources from disturbances and product emissions. Additional fluxes not measured by the inventories, although highly uncertain, could add an additional −239 TgC yr−1 to the inventory-based NA sink estimate, thus suggesting some convergence with the modeling approaches.