Biomimetic scaffolds provide a suitable growth environment for tissue engineering and demonstrate good potential for application in biomedical fields. Different-sized copolymerized biomimetic scaffolds degrade differently, and the degradation rate is affected by the copolymerization ratio. The study of the degradation property is the foundational research necessary for realizing individualized biomimetic scaffold design. The degradation performance of polyesters with different copolymerization ratios has been widely reported; however, the modeling of this performance has been rarely reported. In this research, the degradation of copolymers was studied with multi-scale modeling, in which the copolymers were dispersed in a cellular manner, the chain break time was simulated, and the chain selection was based on the Monte Carlo (MC) algorithm. The probability model of the copolymer’s chain break position was established as a "roulette" model, whose probability values were estimated by the calculation of the potential energy difference at different chain break positions by molecular dynamics that determined the position of chain shear, thereby fully realizing the simulation of the chain micro-break process. The diffusion of the oligomers was then calculated using the macro diffusion equation, and the degradation process of the copolymer was simulated by three-scale coupling calculations. The calculation results were in good agreement with the experimental data, demonstrating the effectiveness of the proposed method.