Despite being recognized as a promising technique for treating high salinity water, membrane distillation (MD) has been plagued by the scaling of sparingly soluble salts. The growth of crystals can not only create additional resistance to evaporating water at the feed-membrane interface, but also alter the hydrophobic network to bridge the feed and distillate (i.e., result in the phenomenon of wetting). When recognizing the uncertain behaviors of calcium sulfate (CaSO4) scaling in MD, this study was motivated to ascertain whether the crystal-membrane interactions could be dependent on the variation in crystalline morphology. In particular, optical coherence tomography (OCT) was employed to characterize the scaling-induced wetting via a direct-observation-through-the-membrane (DOTM) mode, which mitigated the effects of developing an external scaling layer on resolving the crystal-membrane interactions. The improved in-situ characterization suggests that the crystalline morphology of CaSO4 could be effectively regulated by varying the stoichiometry of crystallizing ions; the richness of calcium in the aqueous environment for crystallization would be in favor of weakening the crystal-membrane interactions. The stoichiometry-dependent growth of CaSO4 crystals can be exploited to develop an effective strategy for preventing the hydrophobic network from being wetted or irreversibly damaged.