Abstract Pore structure characteristics of cementitious materials play a critical role in the transport properties of concrete structures. This paper develops a novel framework for modeling chloride penetration in concrete, considering the pore structure‐dependent model parameters. In the framework, a multi‐scale transport model was derived by linking the chloride diffusivities with pore size distributions (PSDs). Based on the three‐dimensional (3D) microstructure generated by “porous growth” and “hard core‐soft shell” methods, two sub‐models were computationally developed for determining the multi‐modal PSDs and pore size‐related chloride diffusivities. The predicted results by these series of models were compared with corresponding experimental data. The results indicated that by adopting pore size‐related diffusivities, even if the total porosities were the same, the proposed multi‐scale chloride transport model could better capture the effect of different PSDs on chloride penetration profiles, while the model without pore structure‐depended parameters would ignore the differences. Compared with the reference transport models, which adopt averaged chloride diffusivities, the chloride penetration depths predicted by the proposed multi‐scale model are in better agreement with experimental data, with 10%–25% reduced prediction error. This multi‐scale transport model is hoped to provide a novel computational approach on 3D microstructure generation and better reveal the underlying mechanism of the chloride penetration process in concrete from a microscopic perspective.