CO2 flooding is essential for significantly enhancing oil recoveries and long‐term CO2 storage. We performed CO2 flooding experiments on target tight cores obtained from Honghe oilfield to investigate the water–rock interaction during CO2 flooding. In addition, we investigate the impact of mineralization and CO2 injection patterns on the sweep efficiency and CO2 long‐term storage using numerical simulations. Results show target core samples are composed of calcite, quartz, Na‐feldspar, and K‐feldspar. In particular, the main water–rock interactions during CO2 flooding are calcite and Na‐feldspar dissolution. The impact of water–rock interactions on the reformation of the matrix is not significant. However, such water–rock interactions will decrease the permeability of the natural fracture system near injection wells, which will lead to the enhancement of CO2 flooding efficiency in fractured formations. In addition, results show that water alternating gas injection will enhance oil recovery and CO2 primary storage. After CO2 flooding, mineral‐trapped CO2 is only 0.53wt.% of the total CO2 storage. As the flooding time increases, the mineral‐trapped CO2 increases. Results show that mineral‐trapped CO2 is 31.08% of the total CO2 storage at the simulation time of 500 years. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.