The hydrodesulfurization process is one of the cornerstones of the chemical industry, removing harmful sulfur from oil to produce clean hydrocarbons. The reaction is catalyzed by the edges of MoS₂ nanoislands and is operated in hydrogen-oil mixtures at 5–160 bar and 260–380 °C. Until now, it has remained unclear how these harsh conditions affect the structure of the catalyst. Using a special-purpose high-pressure scanning tunneling microscope, we provide direct observations of an active MoS₂ model catalyst under reaction conditions. We show that the active edge sites adapt their sulfur, hydrogen, and hydrocarbon coverages depending on the gas environment. By comparing these observations to density functional theory calculations, we propose that the dominant edge structure during the desulfurization of CH₃SH contains a mixture of adsorbed sulfur and CH₃SH.