Clays are commonly used as liners in urban landfills. However, the reactive processes with landfill leachates, and in particular the role of accessory minerals is poorly known. The aim of this work is to evaluate the diffusion of a synthetic urban landfill leachate through compacted natural smectite-illitic clays containing carbonates and sulfates and to predict the functioning of the clay liner for different minor mineral proportions. The leachate, characterized by acidic pH conditions and high organic matter content, is a typical aqueous solution formed in the acetogenic phase of organic matter degradation in urban landfill areas. Medium-scale (11 cm) laboratory diffusion tests were performed over 77 days. Chloride diffusion coefficients, porosity changes, cation exchange constants and the sulfate reduction rate were quantitatively assessed by means of reactive transport modelling. The exchange capacity of the clays is responsible for retention. However, the presence or absence of gypsum in the initial clay rock controls the functioning of the liner. Gypsum dissolution ensures a high sulfate concentration in the porewater and enhances the acetate consumption via sulfate reduction. Gypsum dissolution and the concomitant calcite precipitation do not significantly alter the porosity of the clay rock.