Crystal nucleation from solution plays an important role in environmental, biological, and industrial processes and mainly occurs at interfaces, although the mechanisms are not well understood. We performed nucleation experiments on glycine aqueous solutions and found that an oil–solution interface dramatically accelerates glycine nucleation compared to an air–solution interface. This is surprising given that nonpolar, hydrophobic oil (tridecane) would not be expected to favor heterogeneous nucleation of highly polar, hydrophilic glycine. Molecular dynamics simulations found significantly enhanced vs depleted glycine concentrations at the oil–solution vs air–solution interfaces, respectively. We propose that this interfacial concentration effect facilitates heterogeneous nucleation, and that it is due to dispersion interactions. This interface effect is distinct from previously described mechanisms, including surface functionalization, templating, and confinement and is expected to be present in a wide range of solution systems. This work provides new insight that is essential for understanding and controlling heterogeneous nucleation.