Efficient and accurate prediction of chloride concentration distribution in concrete is extremely important for evaluating the durability of reinforced concrete (RC) structures in the coastal region. A peridynamic (PD) framework for chloride diffusion–reaction is proposed to explore the mechanisms of the long-term chloride ingress in concrete. Specifically, the improved intermediately homogenized peridynamic (IH-PD) method is substituted for the solid modeling method of the interface transition zone (ITZ), with the consideration of the mesoscopic characteristics of concrete and great computational efficiency. In addition, considering the effect of concrete mesostructure, an effective chloride diffusion coefficient is constructed based on the Mori–Tanaka method, in which the proportion of various bonds is determined by the statistics. To verify the reliability of the proposed model, the numerical results are compared with the third-party experiments data. From the results, the randomness of concrete mesostructure leads to the randomness of chloride concentration at the same ingress depth, following the normal distribution. Moreover, the chloride diffusion performance which reflects the speed of chloride diffusion is significantly improved with the increase in the water-cement ratio. Noteworthily, the ITZ thickness can be appropriately increased without affecting the reliability of the results.