Wetting of poly- and mono-crystalline MgO substrates by molten La was investigated at 1323 K in a high vacuum using a modified sessile drop method. The wettability seems to depend mildly on the substrate orientation but strongly on the surface roughness. The initial contact angles on the smooth (100), (110), and (111) surfaces are 63° ± 1°, 69° ± 1°, and 69° ± 1°, respectively, while on the rough polycrystalline surfaces they are much larger (104° ± 3°). The wetting behavior is dictated by the disruption of the oxide film covering the La surface, the extent of the interfacial reaction and the evolution of the reaction product. A thick layer of La2O3 phase formed at the interface and then enwrapped the liquid surface, leading to the recession and warping of the triple line and finally the deterioration in the wettability. On the other hand, magnesium was displaced by the reaction and its evaporation provided additional impetus for the movement of the triple line. Due to different reaction intensities, the wetting behavior of La on the different orientations of the MgO surfaces also showed some discrepancies.