Isotopic fractionation of cationic species during diffusive transport provides novel means of constraining the style and timing of metamorphic transformations. Here we document a major (~1‰) decrease in the Mg isotopic composition of the reaction front of an exhumed contact between rocks of subducted crust and serpentinite, in the Syros mélange zone. This isotopic perturbation extends over a notable length-scale (~1 m), implicating diffusion of Mg through an intergranular fluid network over a period of ~100 kyr. These novel observations confirm models of diffusion-controlled growth of reaction zones formed between rocks of contrasting compositions, such as found at the slab-mantle interface in subduction zones. The results also demonstrate that diffusive processes can result in exotic stable isotope compositions of major elements with implications for mantle xenoliths and complex intrusions.