Isotope disequilibrium is increasingly recognized during crustal anatexis, which is usually attributed to stoichiometry or peritectic phases of melting reactions. Instead, whether fluid influx can contribute to isotope disequilibrium during fluid-fluxed melting remains poorly constrained. Here we report combined Mg-O-Sr isotopic data for migmatites in the Dabie orogen. Leucosomes show considerably lower δ26Mg (−0.71‰ ∼ −0.23‰) and δ18O (3.7‰ ∼ 7.9‰) but higher 87Sr/86Sr(i) (0.7089–0.7131) than the corresponding melanosomes (−0.29‰ ∼ −0.11‰, 6.9‰ ∼ 10.6‰ and 0.7080–0.7119, respectively). Such isotopic difference between leucosomes and melanosomes cannot result from either fractional crystallization, equilibrium, incongruent to non-modal melting or accumulation. Instead, co-variations of δ18O, δ26Mg and 87Sr/86Sr(i) of leucosomes indicate influx of external fluids and their preferential partition into melts. The external fluids could have low δ18O and δ26Mg but high 87Sr/86Sr(i) and were most likely derived from dehydration of the surrounding eclogites and gneisses with Neoproterozoic protoliths experienced meteoric-hydrothermal exchange. One leucosome is plotted off the major trend by its rather low δ26Mg (∼ −0.71‰), and may have been overprinted by inter-diffusion. Simple diffusion modeling shows that the preservation of Mg-O-Sr isotope disequilibrium in the Dabie migmatites requires a short duration from fluid-fluxed anatexis to re-solidification (i.e., < 103–104 years). This study highlights that a combination of multiple isotopes may be conducive to understand the mechanism of disequilibrium melting.