Hydrated (with D2O and H2O) sodium tetrasilicate glasses, quenched from melts at 1400 °C and 1.5 GPa, are studied using 1H, 2H, and 29Si solid-state nuclear magnetic resonance (NMR) spectroscopy. Whereas D2O and H2O depolymerize the silicate melt to similar degrees, protium and deuterium intramolecular partitioning between different molecular sites within the glasses is very different and exemplified by a strong preferential association of deuterons to sites with short O-D…O distances. This preference is independent of total water content and D/H ratio. Substantially different intramolecular D-H partitioning is also observed in a glass with a model hydrous basalt composition. Such large differences in isotope partitioning cannot result from classic equilibrium fractionation because of the high synthesis temperature. Potential kinetic isotope effects are excluded via a slow quench experiment. The apparent fractionation is likely governed by density/molar volume isotope effects, where deuterium prefers sites with smaller molar volume. Large differences in intramolecular site partitioning in melts could lead to significant differences in D-H partitioning between water-saturated melt and exsolved aqueous fluid (where D/HW,Melt ≠ D/HW,Fluid) during crystallization of Earth’s magma ocean, potentially controlling the D/H content of the Earth’s oceans.