Abstract Background Human activities have diverse and profound impacts on ecosystem carbon cycles. The Piedmont ecoregion in the eastern United States has undergone significant land use and land cover change in the past few decades. The purpose of this study was to use newly available land use and land cover change data to quantify carbon changes within the ecoregion. Land use and land cover change data (60-m spatial resolution) derived from sequential remotely sensed Landsat imagery were used to generate 960-m resolution land cover change maps for the Piedmont ecoregion. These maps were used in the Integrated Biosphere Simulator (IBIS) to simulate ecosystem carbon stock and flux changes from 1971 to 2010. Results Results show that land use change, especially urbanization and forest harvest had significant impacts on carbon sources and sinks. From 1971 to 2010, forest ecosystems sequestered 0.25 Mg C ha −1 yr −1 , while agricultural ecosystems sequestered 0.03 Mg C ha −1 yr −1 . The total ecosystem C stock increased from 2271 Tg C in 1971 to 2402 Tg C in 2010, with an annual average increase of 3.3 Tg C yr −1 . Conclusions Terrestrial lands in the Piedmont ecoregion were estimated to be weak net carbon sink during the study period. The major factors contributing to the carbon sink were forest growth and afforestation; the major factors contributing to terrestrial emissions were human induced land cover change, especially urbanization and forest harvest. An additional amount of carbon continues to be stored in harvested wood products. If this pool were included the carbon sink would be stronger.