The strength of jointed rock is a fundamental factor in the slope stability of rock mass. This research investigates the effect of infill thickness on the strength of jointed rock specimens. Unlike previous studies involving artificial rock-like materials and saw-tooth surfaces, this work has been conducted on two natural types of sandstone with various rock surfaces. Natural low-plasticity clay of different thicknesses (1 mm to 3 mm) was used as the infill material. A series of shear box tests with a range of initial normal stresses from 0.5 MPa to 1.5 MPa were performed to obtain high-quality data regarding the shear strength of natural rock and to provide insights into the effect of infill and rock surface roughness on shear strength. The obtained results were also used to improve the current methods of rock strength predictions, which were initially designed to estimate the strength of artificial rock-like material. Based on the obtained laboratory data and the strength estimation using different methods, a newly proposed procedure was proved to provide more accurate estimations of the shear strength of jointed rock.