Formation pore structure and reservoir parameters change continually during waterflooding due to sand production, clay erosion, and pressure/temperature variation, which causes great challenge in geological modeling and simulation. In this work, the XA Oilfield, a block with more than 20 years’ waterflooding history, is used as an example to better understand the fundamental evolution mechanisms of reservoir pore network characteristics over long time waterflooding. We performed a large number of core analyses and experiments to obtain formation parameters (e.g., permeability, porosity, relative permeability, and etc.) at different development stages. The comparison illustrates that reservoir permeability can not only decrease with clay plugging, but also increase by the detachment of fine particles and even the destruction of microscopic structure. We also observed that the point/line contacts among grains decreases, the pore network connectivity increases, the clay content reduces and the rock trends to be more hydrophilic with increasing water injection. Moreover, we developed a pore network model to simulate the variation of formation parameter. The model parameters are also compared and analyzed to get a qualitative understanding of the evolvement laws, which will provide a useful guidance for reservoir accurate modeling.