Abstract Pore-scale mechanism of the waterflooding process contributes to enhanced oil recovery, which has been widely emphasized in the petroleum industry. In this paper, pore-scale waterflooding experiments are carried out on mixed-wetted natural sandstone and 3D printed sandstone using micro-computed tomography (μ-CT). The high-resolution images of oil/water distribution in different stages of waterflooding cycles are acquired. The classification of residual oil after waterflooding is conducted using the shape factor and Euler number, which represents the shape and spatial connectivity, respectively. The in situ contact angles are measured on the segmented images and the pore-scale wettability of these two samples is analyzed. Then, the effects of pore structure, micro-fracture and wettability on the distribution of the patterns of residual oil are analyzed. The results indicate that the types of isolated, cluster, network, and film (only for natural sample) are the main forms of residual oil patterns after the waterflooding process. The negative correlation between the shape factor and the Euler number of the typical oil blocks are presented. The effect of wettability and pore geometry on the morphology of the oil/water interface is quantitatively studied. The capillary pressure is the key factor for the formation of the residual oil blocks, the morphology of which is controlled by both wettability and pore geometry.