Desulfurization of thiophene and its hydrogenated derivatives on Pt(111) are studied using self-consistent periodic density functional theory (DFT), and the hydrodesulfurization network is mapped out. On Pt(111), thiophene has two types of adsorption configurations (parallel cross-bridge and partially tilted bridge-hollow), and for its hydrogenated derivates, the molecule is gradually lifted up from the surface with the addition of hydrogen atoms. In all the adsorbed thiophenic compounds, the S atom is always sp3 hybridized; the C atom in the methylene group is always sp3 hybridized, whereas it is either sp2 or sp3 hybridized in the methyne group, depending on how the group interacts with the surface Pt atoms. On the basis of the thermodynamic and kinetic analysis of the elementary steps, a direct desulfurization pathway is proposed for the hydrodesulfurization of thiophene on Pt(111). In contrast to the common thought that hydrogenation toward aromatic organosulfur compounds would make desulfurization easier, the present work clearly demonstrates that hydrogenations of thiophene on Pt(111) do not reduce the energy barrier for the C–S bond cleavage.