The molecular-scale understanding of the genesis of the MoS2 phase from Mo-oxide precursors supported on alumina is highly challenging with a strong impact on the activation process of heterogeneous industrial catalysts. By means of density functional theory (DFT), we quantify the activation free energies of the elementary steps involved in the sulfo-reduction mechanisms of Mo-trioxide oligomers and the stability of the corresponding Mo-oxysulfide intermediates supported on the γ-alumina (1 0 0) surface. The Gibbs free energy profiles highlight the characteristic chemical reactivity of various oxygen sites involved in the O/S exchange mechanism and reveal that interfacial oxygen atoms (Mo-O-Al) are the most challenging sites to be exchanged with S. We quantitatively compare the two main paths proposed experimentally: the one involving Mo-oxysulfide and Mo-trisulfide intermediates and the second one involving only Mo-oxysulfide. While O/S exchange requires moderate activation energies, the rate-determining steps correspond to S- and O-removal on small MonO3n-xSx or MonS3n (n ≤ 3) oligomeric intermediates. To overcome these high energy steps, the small Mo-trisulfide (MonS3n) oligomers are proposed to be fast diffusing surface species and to promote the growth process towards the targeted MoS2 phase. A reconstruction from a chain to a triangular Mo3S9 conformer also facilitates this phase transformation.