The investigation of layered rock mechanical properties is important for rock stability analysis. To examine the effects of layer inclination angle (LIA) and layer thickness (LT) on the compressive mechanical properties and damage mechanism of layered rock, this paper proposes a new method of preparing layered rock specimens using similar materials and conducting uniaxial compression tests. At the same time, PFC2D numerical analysis software is used to establish the discrete element numerical model of layered rock under uniaxial compression to deepen its microscopic damage mechanism. The results show that the LIA significantly affects the anisotropic mechanical properties of the rock, and the different LIA lead to significant differences in the crack extension paths and failure modes, which can be summarized into four types of cracks and four failure modes. The increase in LT under the effect of different LIA shows different mechanisms of action, which is enhanced in 0° and 90°, weakened in 45° and 75°, and insignificant in 15°, 30° and 60°. In addition, the expansion of micro-cracks in layered rocks are all dominated by interlayer shear cracks first, and then conduct to the rock portion to tensile cracks. The findings of this research offer valuable insights for stability assessment and design of layered rock structures in engineering applications.