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By using a climate system model of intermediate complexity, we have simulated long-term natural climate changes occurring over the last 9000 years. The paleo-simulations in which the model is driven by orbital forcing only, i.e., by changes in insolation caused by changes in the Earth’s orbit, are compared with sensitivity simulations in which various scenarios of increasing atmospheric CO2 concentration are prescribed. Focussing on climate and vegetation change in northern Africa, we recapture the strong greening of the Sahara in the early and mid-Holocene (some 9000-6000 years ago), and we show that some expansion of grassland into the Sahara is theoretically possible, if the atmospheric CO2 concentration increases well above pre-industrial values and if vegetation growth is not disturbed. Depending on the rate of CO2 increase, vegetation migration into the Sahara can be rapid, up to 1/10th of the Saharan area per decade, but Could not exceed a coverage of 45%. In our model, vegetation expansion into today’s Sahara is triggered by an increase in summer precipitation which is amplified by a positive feedback between vegetation and precipitation. This is valid for simulations with orbital forcing and greenhouse-gas forcing. However, we argue that the mid-Holocene climate optimum some 9000 to 6000 years ago with its marked reduction of deserts in northern Africa is not a direct analogue for future greenhouse-gas induced climate change, as previously hypothesized. Not only does the global pattern of climate change differ between the mid-Holocene model experiments and the greenhouse-gas sensitivity experiments, but the relative role of mechanisms which lead to a reduction of the Sahara also changes. Moreover, the amplitude of simulated vegetation cover changes in northern Africa is less than is estimated for mid-Holocene climate.