Geological carbon dioxide storage is one of the most effective technologies to reduce greenhouse gas emissions to the atmosphere. The mineral dissolution is inevitable during the long-term storage process, while the chemical effect on fault slip behavior remains poorly understood. In this paper, we present a hydro-chemical–mechanical coupled fault reactivation study using the unified pipe-interface element method (UP-IEM). The impact of chemical dissolution on stress redistribution is considered. The accuracy of the numerical method to simulate reactive solute transport and fault frictional slip are confirmed by analytical solution and numerical verification. Two different fault tectonic scenarios, of which fault locating in the caprock and fault crosscutting the reservoir and caprock, are designed to investigate the fault slip behavior induced by mineral dissolution. The effect of dissolved CO2 solute concentration, fault aperture, reservoir permeability and chemical reaction rate are discussed. Results show that fault locating in the caprock is easier to be activated. The chemical reaction has a more significant effect on fault slip behavior than fluid pressure during the long-term low-velocity CO2 leakage. The increase of CO2 solute concentration and reservoir reaction rate cause an obvious growth on fault slip displacement. The decrease of fault initial aperture results in the fault slip velocity slower and the slipping area smaller. The high-permeability reservoir keeps the fault more stable than low-permeability reservoir under the influence of mineral dissolution.