© 2017 N. Kampman. Storage of anthropogenic CO2 in geological formations relies on impermeable caprocks as the primary seal preventing buoyant super-critical CO2 escaping. Although natural CO2 reservoirs demonstrate that CO2 may be stored safely for millions of years, uncertainty remains in predicting how caprocks will react with acid CO2-bearing brines. This uncertainty poses a challenge to the assessment of carbon capture and storage schemes. Prediction of caprock behaviour is based primarily on theoretical modelling and laboratory experiments. However, the reactive transport phenomena cannot be reproduced in laboratory experiments over sufficient timescales, theoretical models need calibration against observational data and existing studies on natural caprocks have not resolved mineral reactions. Here we report a detailed description of a stacked sequence of CO2 reservoir-caprock systems exposed to CO2-rich fluids over ∼ 105 years, a time-scale comparable with that needed for effective geological carbon storage. Fluid-mineral reactions in the base of multiple caprocks is driven by diffusion of CO2 and minor H2S from the underlying reservoirs. The reactions include dissolution of hematite, dolomite and K-feldspar and precipitation of Fe-bearing dolomite, gypsum, pyrite and illite over centimetre length-scales. The mineral dissolution reactions generate transient increases in porosity, as determined by neutron scattering measurements, but the propagation of mineral reaction fronts is retarded by the reaction stoichiometry and mineral precipitation. Modelling of the mineral reaction fronts shows that the alteration is sluggish, developing over a >104 year period. The results attest to the significance of transport-limited reactions to the long-term integrity of sealing behaviour in caprocks exposed to CO2.