The randomness and variation of material composition at the meso-scale lead to some limitations in the application of asphalt mixture. When all features are taken into account, the computational effort increases significantly. Therefore, the relationship can be established using the meso-element equivalence method (MEEM). In this paper, the effects of aggregate-asphalt interface, initial void defects and material damage were introduced and MEEM of asphalt mixture was established based on industrial computed tomography (ICT) and finite element method (FEM). The rationality of the model was verified by laboratory performance tests, and the effects of aggregate type, mixture gradation and mesostructural parameters on the mechanical response of MEEM were compared and analyzed. The results showed that the MEEM model captures the mechanical behavior of asphalt mixtures well, the input of visco-elastic material parameters is an important step of MEEM simulation accuracy. The aggregate type, the discrete degree of the skeleton structure and the distribution characteristics of mesostructural parameters are important factors affecting the mechanical properties of asphalt mixture in MEEM.