In this paper, the mechanisms of long‐term CO2 sequestration and the effects of injection modes (including injection temperature, injection rate and injection cycle) in Zhujiang Formation characterized by high porosity and permeability were investigated using the numerical simulation method. Simulation results showed that more than 88% of the injected CO2 would exist in a supercritical state during the injection period and more than 79% of CO2 would be sequestrated in the reservoir by mineral trapping after 5,000 years. Eventually, the distribution shape of SC‐CO2 was a quarter funnel near the injection well, while the distribution shapes of dissolved and mineralized CO2 were both one quarter rotunda. During the long‐term CO2 sequestration in Zhujiang Formation, the dissolved minerals were anorthite, chlorite and smectite in turn, while the top three main precipitated minerals were calcite, dawsonite and albite. Moreover, higher injection temperature leads to a higher mineral tapping and more dissolved/precipitated minerals. While higher injection rate reduces the mineral tapping and total amount of dissolved/precipitated mineral. Compared to injection temperature and injection rate, the injection cycle has little effect on the CO2 phase evolution and mineral dissolution/precipitation process. © 2024 Society of Chemical Industry and John Wiley & Sons, Ltd.