A novel Janus membrane integrating an omniphobic substrate and an in-air hydrophilic, underwater superoleophobic skin layer was developed to enable membrane distillation (MD) to desalinate hypersaline brine with both hydrophobic foulants and amphiphilic wetting agents. Engineered to overcome the limitations of existing MD membranes, the Janus membrane has been shown to exhibit novel wetting properties unobserved in any existing membrane, including hydrophobic membranes, omniphobic membranes, and hydrophobic membranes with a hydrophilic surface coating. Being simultaneously resistant to both membrane fouling and wetting, a Janus membrane can sustain stable MD performance even with challenging feed waters and can thus potentially transform MD to be a viable technology for desalinating hypersaline wastewater with complex compositions using low-grade-thermal energy.