The constant improvement of hydrotreating (HDT) catalysts, driven by industrial and environmentalneeds, requires a better understanding of the interactions between the oxide support (mostly alumina)and the MoS2 active phase. Hence, this work addresses the support-dependent genesis of MoS2 on fourplanar single-crystal a-Al2O3 surfaces with different crystal orientations (C (0001), R ð1 102Þ,M ð1010Þ; and A ð1120Þ). In contrast to classical surface science techniques, which often rely on UHVtypedeposition methods, Mo is introduced by impregnation from an aqueous solution in order to mimicstandard incipient wetness impregnation. Comparison between different preparation routes, impregnationvs. equilibrium adsorption (selective adsorption), is also considered. Atomic force microscopy,X-ray absorption spectroscopy, transmission electron microscopy, and X-ray photoelectron spectroscopyshow that the a-Al2O3 orientation has a clear impact on the strength of metal–support interactions in theoxide state with consequences for the sulfidation, size, stacking, and orientation of MoS2 slabs.Aggregation of molybdenum oxide particles is observed on the C (0001) plane, suggesting weakmetal–support interactions leading to a high sulfidation degree with large slabs. Conversely, the presenceof well-dispersed individual oxide particles on the R ð1 102Þ plane implies stronger metal–support interactions,leading to a low sulfidation degree and shorter MoS2 slabs. Both A ð1120Þ and M ð1010Þ facets,of similar crystallographic structure, display intermediate behavior in terms of sulfidation rate and MoS2size, in line with intermediate metal–support interactions. Polarization-dependent grazing-incidence-EXAFS experiments, as well as high-angle annular dark-field (HAADF) scanning transmission electronmicroscopy analysis, allow us to demonstrate a surface-dependent orientation of MoS2 slabs.Predominant basal bonding is suggested on the C (0001) plane, in agreement with the existence of weakmetal–support interactions. Conversely, a random orientation (edge and basal bonding) is observed forthe other planes. Generalization of these conclusions to industrial catalysts is proposed, based on comparisonof the surface structure of the various model a-Al2O3 orientations used in this work and the predominantlyexposed c-Al2O3 surfaces ((110), (100), and (111)).