Chemical reactions in sliding contacts driven by the combined effects of heat, pressure, and shear underlie the function of lubricant additives that protect surfaces from friction and wear. However, the interplay between thermal and mechanical effects in driving these important reactions, as well as the roles of base oil molecules and the surface chemistry, are not fully understood. In this study, reactive molecular dynamics simulations were used to investigate the reactions between di-tert-butyl disulfide, a component of sulfurized isobutylene extreme pressure additive, and ferrous surfaces in various temperature and stress conditions. Simulations were run with and without a model base oil, n-dodecane, and on either Fe(100) or H-passivated Fe2O3 surfaces. Reaction yield increased with both temperature and pressure for all three model systems. The presence of the base oil did not significantly affect the yield or reaction pathway, but the pressure dependence of the yield was slightly lower because the base oil reduced the shear force on the surfaces. However, replacing the ideal Fe(100) with H-passivated Fe2O3 surfaces led to reaction pathways involving the oxygen from the surface and decreased the reaction yield. The rate-limiting step of the reaction for the three models was then analyzed in the context of the Bell model. Although these observations were made for a specific chemical component of extreme pressure additives, the approach demonstrated can be used for other additive chemistries as well as for interpreting shear-driven reactions more generally within the framework of reactive molecular dynamics simulations.