The wetting of (100), (110), and (111) MgO single crystals by molten Mg was studied in a flowing Ar atmosphere at 1073 K using an improved sessile drop method. The results show that the contact angle and work of adhesion are mildly dependent on MgO substrate orientation. However, the work of separation calculated by density functional theory shows a sequence of (100) < (110) < (111). This discrepancy was explained by a model considering the possible effects of evaporation and deposition of Mg at the substrate surface on the interfacial adhesion. For Mg on the clean MgO surfaces, the adhesion consists primarily of Mg-O ionic bonds with some Mg-Mg metallic bonds. In addition, a small amount of covalent bonds are present in the metal slab adjacent to the Mg/MgO (110) and Mg/MgO (111) interfaces. The different work of separation at three interfaces depends on the strength and amounts of Mg-O and Mg-Mg bonds as well as on the surface free energy of respective planes. For the MgO surfaces pre-deposited by a monolayer of Mg atoms, the interfaces are dominated by the Mg-Mg bonds, thus mitigating the effect of substrate orientation on the wettability and adhesion.