Dispose and utilization of municipal solid waste incinerator bottom ash (MWSIBA) is one of the imperative issues in environmental protection. The applicability of substitution for natural aggregate with MWSIBA in asphalt mixture was investigated by the performance and micro structure of asphalt mixtures with diverse porosity levels of MWSIBA (varying the replacement percentage). The effects of porosity of MWSIBA on asphalt mixture performance were captured by determination of Marshall stability, tensile strength, dynamic stability and the maximum flexural-tensile strain. The horizontal vibration extraction procedure test was implemented for the heavy metal leaching concentration to evaluate the environmental safety of MWSIBA asphalt mixture. Chemical and micro-morphologic characterization for MSWIBA were conducted to explore the mechanism of moisture damage resistance of asphalt mixture. Results indicated that porosity and replacement rate of MWSIBA exerted impacts on properties of asphalt mixture. The rutting resistance of asphalt mixture decreased due to the addition of MWSIBA, resulting in a reduction in high temperature performance. MWSIBA with porosity no less than 19% was beneficial to the improvement of moisture susceptibility and low temperature performance of asphalt mixture, while high mixing amount of MWSIBA was unfavorable to the properties of asphalt mixture. The water immersion stimulated the hydration reaction in MWSIBA, leading to the formation of C-(A)-S-H gel with strong cementation property, which enhanced the adhesion between MWSIBA and asphalt binder. MWSIBA asphalt mixture presented lower heavy metal concentration and better environmental safety than MSWIBA.