Cemented tailings-rock backfill (CTRB) can simultaneously utilize tailings and waste rocks and ensure engineering security in deep mines. However, its mechanical property evolution under waste rock’s influence is still not well understood. This study constructed a novel CTRB mechanical property evolution model with the mass fraction of waste rock and damage coefficient as critical parameters. The laboratory and numerical uniaxial compression tests of cube CTRB specimens with different waste rock contents were conducted to verify the proposed model. Numerical CTRB models with few initial damages simulated by the discrete element method were used to explore the independent effect of initial damage and the meso-mechanism of mechanical property evolution. Results show that the elastic modulus and compressive strength of CTRB increase first and then decrease with the mass fraction of waste rock increasing under the coupling effect of the strengthening of waste rock and weakening of initial damage. The proposed mechanical property evolution model can well reflect this coupling effect and the independent influence of initial damages. Values of model parameters are all within a reasonable range. The change in the number of contacts in CTRB is the mesoscopic reason for the evolution of its mechanical properties. Increasing the waste rock content will increase the amount of particle-to-block contacts that can enhance the mechanical properties of CTRB but also increase the amount of block-to-block contacts which represent initial damages.