We adapted an integrated model, RESPONSE, to assess the cost-optimized timing of oceanic, geological, and biological carbon sequestration versus fossil emission reduction to mitigate climate change in a context of uncertainty and learning about the magnitude of climate sensitivity to greenhouse-gas forcing. We find that the replacement of abatement measures in the energy sector by various sequestration measures can cut total mitigation policy costs by up to 35% for the Intergovernmental Panel on Climate Change (WMO and UNEP) A1B and A2 emissions scenarios. Biological carbon sequestration and carbon capture and geological or oceanic storage (CCS) contribute to relaxing carbon constraints on the energy sector while adapting to the level of climatic uncertainties. Afforestation, the most flexible option, is helpful in the short run to prevent excessively fast warming, while CCS in geologic or oceanic reservoirs is useful primarily in the longer run to mitigate against overshooting a desired temperature ceiling. In cases of leaky storage, CCS may be less appropriate than emission reduction to stabilize climate, especially if high reference emissions and/or high climate sensitivity are expected. Worst-case scenarios of high emissions and climate sensitivity might preclude to a certain extent the use of carbon sequestration as a substitute for fossil energy reductions. Therefore, the design of optimal sequestration policies depends critically on the anticipation of (1) long-term emission trends and (2) the effective value of the climate sensitivity.