In the macroscopic soil mechanic experiment, the occurrence of cracks and failures of clay soil is intimately related to the nanoscale shear behavior of clay mineral sheets, which urgently needs to be studied. The two basal surfaces of kaolinite have different wettabilities with water molecules, thereby playing a significant role in microshear processes. In this article, the molecular dynamics (MD) simulation method was used to study the shear properties of hydrated kaolinite as a function of the water content and wettability Three shear models with different wettability (i.e., the hydrophilicity and hydrophobicity) and water content were established. According to the stick–slip effect of the curves of friction, 1W (one layer of saturated water molecules between clay mineral sheets) is the microplastic limit water content of kaolinite that transitions from brittle failure to ductile failure. By analyzing the basal spacing and the shear viscosity in the hydrophilic/hydrophobic model, the mosaic layer and vacuum layer at the clay–water interface and the condensation behavior of water molecules were observed. The friction of hydrated kaolinite was weakened significantly by the interparticle water film, which decreases by 64.30%–98.38% compared to the dry case. In hydrated kaolinite, the hydrophilic model has the strongest interfacial friction force due to the strong interaction between clay–water. While in dry cases the interfacial friction of the hydrophobic model is not the weakest among the three models, as the interaction between clay–clay has a larger component in the friction direction. Additionally, the hydrophilic/hydrophobic basal surface of hydrated kaolinite exhibits unique shear properties by affecting the interfacial friction, the hydrogen bond effect, and the flow of interparticle water. The simulation study on the shear behavior of hydrated kaolinite explains the microscale failure mechanism of clay soil, which has significance for disaster prevention and reduction projects such as landslide treatment.