Atmospheric measurements and land-based inventories imply that terrestrial ecosystems in the northern hemisphere are taking up significant amounts of anthropogenic cabon dioxide (CO2) emissions; however, there is considerable disagreement about the causes of this uptake, and its expected future trajectory. In this paper, we use the ecosystem demography (ED) model to quantify the contributions of disturbance history, CO2 fertilization and climate variability to the past, current, and future terrestrial carbon fluxes in the Eastern United States. The simulations indicate that forest regrowth following agricultural abandonment accounts for uptake of 0.11 Pg C yr−1 in the 1980s and 0.15 Pg C yr−1 in the 1990s, and regrowth following forest harvesting accounts for an additional 0.1 Pg C yr−1 of uptake during both these decades. The addition of CO2 fertilization into the model simulations increases carbon uptake rates to 0.38 Pg C yr−1 in the 1980s and 0.47 Pg C yr−1 in the 1990s. Comparisons of predicted aboveground carbon uptake to regional-scale forest inventory measurements indicate that the model's predictions in the absence of CO2 fertilization are 14% lower than observed, while in the presence of CO2 fertilization, predicted uptake rates are 28% larger than observed. Comparable results are obtained from comparisons of predicted total Net Ecosystem Productivity to the carbon fluxes observed at the Harvard Forest flux tower site and in model simulations free-air CO2 enrichment (FACE) experiments. These results imply that disturbance history is the principal mechanism responsible for current carbon uptake in the Eastern United States, and that conventional biogeochemical formulations of plant growth overestimate the response of plants to rising CO2 levels. Model projections out to 2100 imply that the carbon uptake arising from forest regrowth will increasingly be dominated by forest regrowth following harvesting. Consequently, actual carbon storage declines to near zero by the end of the 21st century as the forest regrowth that has occurred since agricultural abandonment comes into equilibrium with the landscape's new disturbance regime. Incorporating interannual climate variability into the model simulations gives rise to large interannual variation in regional carbon fluxes, indicating that long-term measurements are necessary to detect the signature of processes that give rise to long-term uptake and storage.