The wetting process of CaO-MgO-Al2O3-SiO2 (CMAS) melt on yttria-stabilized zirconia (YSZ) surface is studied at 1523 K by molecular dynamics simulations. Several parameters, such as the contact angle (theta), work of adhesion, surface tension, and viscosity are systematically calculated and analyzed to estimate the wettability. The results of the contact angle analysis show that the wetting trend of CMAS on YSZ is as follows: YSZ(110) > YSZ (001) > YSZ(111) > YSZ(101) > YSZ(010). The hydrophilicity or hydrophobicity of the YSZ surface models to CMAS is predominantly determined by their surface energies. Some other properties, such as surface tension, viscosity of the CMAS melt, and work of separation of CMAS/YSZ further confirm this conclusion. An in depth study reveals that CMAS shows its highest wettability on the YSZ(110) surface. This interaction originates from the highly energetic Mg, Si, and O ions, especially the Mg ions of CMAS penetrating the YSZ surface layer. The intrinsic driving force for such a strong movement of CMAS ions is stimulated by the oxygen ions on the YSZ (110) surface layer, providing it a higher electronegativity compared to other crystal surfaces. The distribution of oxygen ions on the YSZ surface layer is the key factor affecting the wettability and even corrosion of CMAS on YSZ thermal barrier coatings.