Wettability has a strong influence on multi-phase flow behavior through reservoir rock. Reservoir rocks tend to have spatially varying wettability. Prior to contact with oil, rocks are almost always naturally water-wet. As oil invades the pore-space over geologic time, the initial water-wet state may be altered in certain locations due to adhesion of substances within the oil phase to the grains. Mechanisms of wettability alteration depend on various properties such as pressure, temperature, mineral chemistry, surface roughness and fluid composition. In this study wettability alteration in a reservoir rock is studied through direct simulation using multiphase Lattice Boltzmann method where the computational grid is constructed from segmented micro-CT images of the rock sample. The pore-grain interface is defined by a triangulated surface mesh for accurate fluxes near boundary and local curvature calculation. A capillary pressure drainage simulation is conducted in a water-wet Berea sandstone sample initially filled with water. When oil invades the pore space as the capillary pressure is increased, a fraction of the pore-grain surface is altered towards an oil-wet condition, as determined by a novel wettability alteration process. This process calculates local curvature at every surface element of the rock, obtains local capillary pressure from the simulation and assumes a disjoining pressure to determine water-film breakage at every location of the pore-grain surface. As a result, a spatially varying rock wettability is created. Using this new wettability distribution, the simulation is continued to allow the fluid phases to redistribute accordingly. The process is iteratively carried out until both fluid saturation and wettability distribution converged at a given applied capillary pressure. Afterwards, the pressure is ramped up to the next stage and the process is repeated again. It has been found that the wettability alteration is a slow dynamic process where the non-wetting phase can gradually invade finer pore space as the surrounding grain wettability is altered. In this study, it has also been found that wettability alteration of the reservoir rock produces lower connate water saturation during primary drainage compared to the simulation results without alteration. The resulting spatially varying wettability distribution from primary drainage is used for a subsequent water flooding simulation to calculate water-oil relative permeability curves. The methodology presented in this work can be leveraged to better understand and predict an improved mixed wetting conditions found in the reservoir rocks which is needed for more accurate displacement tests such as relative permeability simulations.