Humans have altered the Earth’s land surface since the Paleolithic mainly by clearing woody vegetation first to improve hunting and gathering opportunities, and later to provide agricultural cropland. In the Holocene, agriculture was established on nearly all continents and led to widespread modification of terrestrial ecosystems. To quantify the role that humans played in the global carbon cycle over the Holocene, we developed a new, annually resolved inventory of anthropogenic land cover change from 8000 years ago to the beginning of large-scale industrialization (ad 1850). This inventory is based on a simple relationship between population and land use observed in several European countries over preindustrial time. Using this data set, and an alternative scenario based on the HYDE 3.1 land use data base, we forced the LPJ DGVM in a series of continuous simulations to evaluate the impacts of ALCC on terrestrial carbon storage during the preindustrial Holocene. Our model setup allowed us to quantify the importance of land degradation caused by repeated episodes of land use followed by abandonment. By 3 ka BP, cumulative carbon emissions caused by anthropogenic land cover change in our new scenario ranged between 84 and 102 Pg, translating to c. 7 ppm of atmospheric CO2. By ad 1850, emissions were 325–357 Pg in the new scenario, in contrast to 137–189 Pg when driven by HYDE. Regional events that resulted in local emissions or uptake of carbon were often balanced by contrasting patterns in other parts of the world. While we cannot close the carbon budget in the current study, simulated cumulative anthropogenic emissions over the preindustrial Holocene are consistent with the ice core record of atmospheric d13CO2 and support the hypothesis that anthropogenic activities led to the stabilization of atmospheric CO2 concentrations at a level that made the world substantially warmer than it otherwise would be.