The pressure-sensitive effect on the pore structure of sandstone was investigated using X-ray computed micro-tomography and QEMSCAN quantitative mineral analysis. In a physical simulation study, we extracted the pore network model from digital cores at different confining pressures and evaluated the effect of pressure sensitivity on the multiphase displacement process. In both the pore network model and QEMSCAN scanning, the pore structure was observed to be damaged under a high confining pressure. Due to their different scales, the pores and throats exhibited inhomogeneous changes; further, the throats exhibited a significant variation compared to that exhibited by the pores. Meanwhile, the heterogeneity of the pore structure under the two aforementioned activities was aggravated by the elastic–plastic deformation of the pore structure. The pressure-sensitive effect increased the proportion of mineral particles, such as quartz (the main component of the core skeleton), and reduced the proportion of clay minerals. The clay minerals were originally attached to the pore walls or interspersed in the pores; however, as the pressure increased, the clay minerals accumulated in the pores resulting in blockage of the pores. While simulating the multiphase displacement process, increasing the confining pressure was observed to severely restrict the flowability of oil and water. This study promises to improve the efficiency of reservoir development in terms of oil and gas exploitation.