The influence of surface topography on the mechanical behavior of soil-structure interfaces over a range of particle sizes and shapes is systematically investigated in this research. 3D printed interfaces with different topographies and uniformly graded 3D printed soil particles and two types of natural sands (Ottawa sand 20/30 and Dolomite sand #1, #2 and #3) were employed and tested. Laboratory investigations showed that the shear strength and volume change responses of the 3D printed interfaces are positively influenced with the increase of the inclination of asperities. The proposed wedge friction model successfully explained the distinct mechanical behaviors of soil-structure interfaces under shearing. A “turning point” was found for the interface shear resistance with the increase of the inclination of asperities. When the surface topography produces passive resistance to the soil, the change of the surface topography has little effect on the interface mechanical behavior. The findings from this research will provide insights for soil-structure interface design and discrete element method (DEM) simulations in considering the mechanical behavior of soil-structure interfaces.