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An effective and safe operation for sequestration of CO2 in coal seams requires a clear understanding of injection-induced coupled hydromechanical processes such as the evolution of pore pressure, permeability, and induced caprock deformation. In this study, CO2 injection into coal seams was studied using a coupled flow-deformation model with a new stress-dependent porosity and permeability model that considers CO2-induced coal softening. Based on triaxial compression tests of coal samples extracted from the site of the first series of enhanced coalbed methane field tests in China, a softening phenomenon that a substantial (one-order-of-magnitude) decrease of Young's modulus and an increase of Poisson's ratio with adsorbed CO2 content was observed. Such softening was considered in the numerical simulation through an exponential relation between elastic properties (Young's modulus and Poisson's ratio) and CO2 pressure considering that CO2 content is proportional to the CO2 pressure. The results of the numerical simulation show that the softening of the coal strongly affects the CO2 sequestration performance, first by impeding injectivity and stored volume (cumulative injection) during the first week of injection, and thereafter by softening mediated rebound in permeability that tends to increase injectivity and storage over the longer term. A sensitivity study shows that stronger CO2-induced coal softening and higher CO2 injection pressure contribute synergistically to increase a significant increase of CO2 injectivity and adsorption, but also result in larger caprock deformations and uplift. Overall, the study demonstrates the importance of considering the CO2-induced softening when analyzing the performance and environmental impact of CO2-sequestration operations in unminable coal seams. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd.