Soil-rock mixture is a commonly used subgrade filling material in high-fill transportation engineering with heterogeneous compositions and complicated mesostructure. A novel degradation model for rock blocks is established based on the Discrete Element Method to capture the compressive behaviors of soil-rock mixtures. The gradual degradation process of rock blocks can be considered, including slight degradation, corner breakage, and fracture. Among them, the simulation method of slight degradation is proposed based on the idea of contact detach, and can reflect the nonlinear stiffness between rock block particles. The simulation of corner breakage adopts a method that considers the size effects and the Weibull distribution of rock strength. And the simulation method for fracture or smash is to search for rock blocks bearing excessive stress and replacing them with breakable clusters. The DEM model was calibrated with the laboratory test result of force–displacement curve in particle compression test. Then, a series of large-scale confining compression test simulations have been carried out to analyze the compression deformation behaviors and particle contact characteristics with different vertical stress and rock block proportion. The results show that for the selected sample, the stiffness is relatively high when the rock content is between 50 and 80%, which can be well explained from a meso-scale perspective.