While the Holocene establishment of agricultural societies led to unprecedented impact on much of the Earth’s vegetation and soils, the importance of preindustrial anthropogenic soil degradation on observed changes in land cover over the Holocene is the subject of lively debate. Here we attempt to quantify the role of the development of agro-pastoral land use systems on global soils and vegetation by driving a global vegetation model with a new scenario of anthropogenic land use and land cover change. Holding all other biotic and abiotic parameters constant, we ran a serious of simulations approximating realistic changes in soil texture, depth, and stoniness as a function of human impact. Our model results show that over the course of the Holocene, human-induced soil degradation led to substantial changes in vegetation cover, particularly in semiarid regions and at biome boundaries. Forests occur on the deepest and least dense soils, while grasslands or deserts develop when soils become very shallow and/or dense. Transition states between these two extremes consist of various types of open woodland and xerophytic shrubland. Both changes in forest cover, which affects aboveground biomass, and changes in soil physical properties, which affect soils’ ability to bind organic matter, have a substantial impact on carbon storage and further suitability for agriculture. Degraded soils that are simulated with lower water holding capacity and lower organic matter content result in lower suitability for crop and pasture, partly feeding back on anthropogenic land use by increasing per capita land use requirements. Our model simulations show that soil degradation leads to certain regions of the world (Mediterranean, South Asia) becoming progressively less productive and suitable for agriculture through the Holocene, resulting in more and more land coming under anthropogenic influence as overall land quality decreases. These results highlight the importance of soils for humanity.