With the advent of increasingly stringent regulations on sulfur containing in oil products, desulfurization of crude oil has become an urgent task for petrochemical production. Molybdenum sulfide (MoS2) have been extensively studied as one of the most efficient hydrodesulfurization catalysts. Co-doped molybdenum sulfides are usually used in desulfurization processes of sulfur-containing compounds, in which the transition metal Co could promote its catalytic performance. Herein, density functional theory was employed to investigate the formation of coordinative unsaturated active sites (CUS) and the catalytic desulfurization process of methanethiol (CH3SH) at the Co-doped MoS2 triangular clusters. Results showed that Co was not the effective reaction site on hydrogenation process, and Mo and S atoms acted as the active sites of hydrogen dissociation during the formation of CUS sites, followed by the H2S generation and desorption. The charge population analyses showed that Co promoted the hydrogenation process indirectly. CH3SH prefered to be adsorbed at the TopCo site with a high adsorption energy of -1.44 eV. The charge population and frontier orbitial analyses illustrated that Co can alter the distribution of the surface atoms' charge and the LUMO orbital of CUS and showed the strong electrophile and thus strengthening the CH3SH adsorption. When CH3SH was adsorbed at the Co-doped MoS2 clusters, electrons transfered from CH3SH to the surface atoms of MoS2. In this work, three desulfurization pathways of CH3SH at the Co-doped MoS2 were investigated, namely, the C-S bond initial scission, the S-H bond initial scissions, and the C-S and S-H scissions simultaneously. The competitive route during the CH3SH desulfurization process started with the S-H and C-S bond scissions successively, followed by the methane formation in the terms of thermodynamics and kinetics, and the formation of methane was the rate-determining step with the energy barrier of 1.51 eV.