The design of the repository for high-level nuclear waste (HLW) in France consists of a multiple-barrier system including steel canisters in a clay host rock. The system will undergo temperature variations in time and space, the heat source being the HLW within the canisters. The effect of a thermal gradient in space on the Fe–claystone interaction was investigated here by applying a thermal gradient (150–300°C and 80–150°C) to a mix of claystone, Fe, and an aqueous chloride solution over periods of 3 and 6 months. Following the reaction, the starting clay minerals (mostly illite and mixed-layer illite-smectite) evolved toward chlorite, Fe-serpentine, Fe-saponite, mixed-layer chlorite-smectite, or mixed-layer serpentine-smectite as a function of temperature. Iron corrosion made the medium basic and reductive. Magnesium enrichment of clay minerals was observed in the hottest part of the experiment due to Mg migration under the thermal gradient. Reaction progress was enhanced at the lowest temperatures, compared to batch experiments.