<p>The rock–concrete bi-material structures, as compositions of a natural construction material (rock) and artificial one (concrete), can be extensively found in civil engineering. The bi-material interface is considered as the weak link affecting the overall safety and stability of rock–concrete structures. The interface cracking behavior is therefore a critical issue for the rock–concrete structures. In this study, rock–concrete specimens with a prefabricated crack along the irregular interface were tested under uniaxial compression. Two new factors are considered in the test specimens: crack closure and interface roughness. The load–displacement responses, acoustic emission (AE) activities and crack closure process were adopted to characterize the mechanical behavior of the tested specimens. A parametric study, including interface roughness, interface inclination angle and concrete strength was also conducted. The results indicated that the interface crack propagation was related to the interface inclination angle and concrete strength. As the interface inclination angle or concrete strength increased, the tensile cracks decreased, and shear cracks became dominant. The strength of the bi-material specimens increased first and then decreased with the interface inclination angle and concrete strength. The specimens’ failure modes included tensile, tensile-shear (equilibrium type), shear-tensile (shear type) and shear failure. A theoretical model considering the crack close stress and interface roughness was then developed based on fracture mechanics to predict the compressive strength of the rock–concrete bi-material specimen. This paper considers the effects of crack closure and complex interfaces in the study of the strength of rock–concrete structures, providing a new approach and method for strength prediction of rock–concrete structures, and has certain reference significance.</p>