Fluids liberated from subducting slabs are critical in global geochemical cycles. We investigate the behaviour of Mo during slab dehydration using two suites of exhumed fragments of subducted, oceanic lithosphere. Our samples display a positive correlation of δ98/95MoNIST 3134 with Mo/Ce, from compositions close to typical mantle (−0.2‰ and 0.03, respectively) to very low values of both δ98/95MoNIST 3134 (−1‰) and Mo/Ce (0.002). Together with new, experimental data, we show that molybdenum isotopic fractionation is driven by preference of heavier Mo isotopes for a fluid phase over rutile, the dominant mineral host of Mo in eclogites. Moreover, the strongly perturbed δ98/95MoNIST 3134 and Mo/Ce of our samples requires that they experienced a large flux of oxidised fluid. This is consistent with channelised, reactive fluid flow through the subducted crust, following dehydration of the underlying, serpentinised slab mantle. The high δ98/95MoNIST 3134 of some arc lavas is the complement to this process.