In this work, we have investigated the activation process and structure of Ni-promoted MoxW(1-x)S2/Al2O3 hydrodesulfurization (HDS) catalysts. Conversion of Mo and W oxides to the catalytically active MS2 (M = Mo, W) phase by sulfidation in gaseous H2S/H2 proceeded via different pathways, as found by XPS and EXAFS. The slower sulfidation kinetics of W on the alumina support formed NiMoxW(1-x) sulfides with a two-dimensional core-shell structure. Mo was mostly located in the core and W in the shell, as evidenced by EXAFS. Increasing the H2S/H2 pressure during sulfidation distributed Mo and W more homogeneously in the metal sulfide particles. This was attributed to the more favorable sulfidation of W under these conditions (i.e., below the temperature of MoS2 formation). Catalytic testing was in line with these findings and demonstrated that a core-shell structure is the active phase in thiophene HDS (1 atm), whereas a homogeneously mixed MS2 phase catalyzes the HDS of dibenzothiophene at 40 bar. This is the first example of a core-shell structure in promoted MoxW(1-x)S2 catalysts. Support interactions in the oxidic precursor, which affect the sulfidation kinetics, were found to play a key role in the formation of these structures.