Abstract The multifield coupling response and mechanism is directly related to the enhancement of oil recovery and CO2 storage in ultralow-permeability oil reservoir, considering the CO2/water flooding. In this study, multifield morphology and multiphase evolution was investigated through the developed FLAC3D-TOUGHREACT simulator, considering the large-scale CO2 flooding, water flooding and CO2-Alatering-water flooding (CAWF) scenarios, and mechanical response and petrophysical properties was analyzed. The results show that formation pressure is sensitive to CO2 flooding with early initiation and dynamic increase response with maximum value of 11.5 MPa in CO2 flooding and 9.5 MPa in CAWF, while that immunity for the water flooding with later initiation and slight increase response. The CO2 expansion and CO2-water-formation interaction dominate the decrease of in-situ stress and lead to the pronounced enhancement of permeability about 3 times, and the dissolved water in formation resulted in the slow increase of formation pressure. And a slight temperature reduction of 0.5–2 °C was observed. In addition, formation porosity is more sensitive to the injected CO2 than water, while the injected water promoted the violent reaction of CO2-water-formation with the enhancement of mineral dissolution and larger increase rate of porosity. The slight response of permeability followed by the dynamic increase induced by the enlarge pore size followed by the pore connectivity under the combined chemical and physical effects of water/CO2, and the percentage of dissolution for the calcite reduced by 0.08%. The findings provided significant reference to the simulation and engineering practice.