Sedimentary rocks with alternating mudstone and sandstone sequence are susceptible to landslides even under very gentle slope inclinations. Continued occurrences of such landslides in Nanjiang, South Western part of China, bring out the necessity for more understanding of their failure mechanism. In this study, we present a series of investigations on the physical, chemical, and mechanical characteristics of weak interlayers during their formation at landslide slip surfaces, both in macro- and microscales. Our field investigations at these deep-seated landslides revealed the presence of extensive weak interlayers of clay in between alternating sandstone mudstone formations. Tectonic processes combined with loading and unloading effects and strain incompatibility might lead to the argillization of rock by easing water intake, which leads to the formation of these weak layers. We studied how changes in material microstructures, mineral composition, and ionic concentrations during the formation process (argillization) might cause a fall in mechanical strength. We found that degradation of mechanical resistance takes place even at the initial stages of argillization and shear strength of the weak layers decreases proportionally to the time of saturation and argillization.