In this study, the synergy effect of biheteroatoms (ZrOx and CeOy) and a Ni promoter on the catalytic performance of MoS2 crystallites grafted on SBA-15 silica for the hydrodesulfurization (HDS) of dibenzothiophene (DBT) in diesel was investigated. The pyridine-Fourier transform infrared (py-FTIR) spectroscopy, ammonia temperature-programmed desorption (NH3-TPD), and X-ray photoelectron spectroscopy (XPS) analyses revealed that the surface acidity, number of active sites, and the dispersion of MoS2 crystallites increased significantly with the incorporation of ZrOx and CeOy on SBA-15 than other supported catalysts evaluated. The ZrOx–CeOy–SBA-15-supported NiMo catalyst could remove 59% of DBT in diesel spiked with 1000 ppm of DBT after 1 h of reaction and up to 96% of DBT after 5 h of reaction. Density functional theory (DFT) simulations further gave interesting insights; a thin-film model of SBA-15 decorated with Zr and Ce indicates that the metal sites induced a strong hydrogen bond network leading to higher surface stability. Furthermore, Ce grafted on SBA-15 enhanced the adsorption of water molecules that increases the Bro̷nsted acid sites and subsequently improved its catalytic efficiency. DFT simulation of thiophene HDS showed a stepwise rupture of thiophene C–S bonds with the second C–S bond breaking as the plausible rate-determining step.