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Mineral scaling constrains membrane distillation (MD) and limits its application in treating hypersaline wastewater. Addressing this challenge requires enhanced fundamental understanding of the scaling phenomenon. However, MD scaling with different types of scalants may have distinctive mechanisms and consequences which have not been systematically investigated in the literature. In this work, we compared gypsum and silica scaling in MD and demonstrated that gypsum scaling caused earlier water flux decline and induced membrane wetting that was not observed in silica scaling. Microscopic imaging and elemental mapping revealed contrasting scale morphology and distribution for gypsum and silica, respectively. Notably, while gypsum crystals grew both on the membrane surface and deep in the membrane matrix, silica only formed on the membrane surface in the form of a relatively thin film composed of connected submicrometer silica particles. We attribute the intrusion of gypsum into membrane pores to the crystallization pressure as a result of rapid, oriented crystal growth, which leads to pore deformation and the subsequent membrane wetting. In contrast, the silica scale layer was formed via polymerization of silicic acid and gelation of silica particles, which were less intrusive and had a milder effect on membrane pore structure. This hypothesis was supported by the result of tensile testing, which showed that the MD membrane was significantly weakened by gypsum scaling. The fact that different scaling mechanisms could yield different consequences on membrane performance provides valuable insights for the future development of cost-effective strategies for scaling control.