Large amounts of carbon (C) have been released into the atmosphere over the past centuries. Less than half of this C stays in the atmosphere. The remainder is taken up by the oceans and terrestrial ecosystems. Where does the C come from and where and when does this uptake occur? We address these questions by providing new estimates of regional land-use emissions and natural carbon fluxes for the 1700–2000 period, simultaneously considering multiple anthropogenic (e.g. land and energy demand) and biochemical factors in a geographically explicit manner. The observed historical atmospheric CO₂ concentration profile for the 1700 to 2000 period has been reproduced well. The terrestrial natural biosphere has been a major carbon sink, due to changes in climate, atmospheric CO₂, nitrogen and management. Due to land-use change large amounts of carbon have been emitted into the atmosphere. The net effect was an emission of 35 Pg C into the atmosphere for the 1700 to 2000 period. If land use had remained constant at its distribution in 1700, then the terrestrial C uptake would have increased by 142 Pg C. This overall difference of including or excluding land-use changes (i.e. 177 Pg C) comes to more than half of the historical fossil-fuel related emissions of 308 Pg C. Historically, global land-use emissions were predominantly caused by the expansion of cropland and pasture, while wood harvesting (for timber and fuel wood) only played a minor role. These findings are robust even when changing some of the important drivers like the extent of historical land-use changes. Under varying assumptions, land-use emissions over the past three centuries could have increased up to 20%, but remained significantly lower than from other sources. Combining the regional land-use and natural C fluxes, North America and Europe were net C sources before 1900, but turned into sinks during the twentieth century. Nowadays, these fluxes are a magnitude smaller than energy- and industry-related emissions. Tropical regions were C neutral prior to 1950, but then accelerated deforestation turned these regions into major C sources. The energy- and industry-related emissions are currently increasing in many tropical regions, but are still less than the land-use emissions. Based on the presented relevance of the land-use and natural fluxes for the historical C cycle and the significance of fossil-fuel emissions nowadays, there is a need for an integrated approach for energy, nature and land use in evaluating possible climate change mitigation policies.