Drying process of porous medium is of interest in engineering applications. However, pore-scale studies of wettability effects on the drying process of three-dimensional (3D) porous media remain limited. X-ray microtomography was used to investigate the wettability effects on the drying process of 3D porous medium from a pore-scale perspective. Results show higher wettability increases capillary pressure, which enhances the rearrangement of liquid from large pores to small pores. We also found that liquid clusters are unlikely to disappear for a long time confirming that higher wettability supports the flow through liquid film. This study also provides new insight that capillary flow by liquid film is associated with branch clusters. These clusters maintain the gas–liquid interfacial area that acts as the evaporation surface. As a result, drying is intensive in a water-wet porous medium with a longer constant rate period in which drying is controlled by external diffusion. In a neutral-wet porous medium, an early drop in drying rate occurs. Thus, drying is mainly a falling rate period limited by vapor diffusion through the newly emerging dried region within the medium.