Membrane distillation (MD) is emerging as an important desalination technology that can operate at relatively low temperatures and can handle high salt concentrations. In this Article, we present microwave-induced membrane distillation (MIMD) where microwave radiation is used to heat the saline water for MD. Pure water vapor flux from MIMD was compared to that generated by conventional heating, and the enhancement reached as high as 52%. Because of the higher dielectric constants, flux enhancement was more significant at high salinity, and the mass transfer coefficient at 150 000 ppm was found to be nearly 99% higher than what was observed under conventional heating. Performance enhancement in MIMD was attributed to nonthermal effects such as the generation of nanobubbles, localized superheating, and breaking down of the hydrogen-bonded salt–water clusters. These effects were investigated using FTIR, ion mobility measurements, and dynamic light scattering. In addition, microwave heating consumed nearly 20% less energy to heat water to the same temperature. The combination of energy savings and higher flux represents a significant advancement over the state of the art for MD.