Abstract The physical and chemical properties of atomically thin two-dimensional (2D) materials can be modified by the substrates. In this study, the substrate effect on the electrocatalytic hydrogen evolution reaction (HER) in 2D Mo 2 C monolayers was investigated using first principles calculations. The isolated Mo 2 C monolayer shows large variation in HER activity depending on hydrogen coverage: it has relatively low activity at low hydrogen coverage but high activity at high hydrogen coverage. Among Ag, Au, Cu, and graphene substrates, the HER activity is improved on the Ag and Cu substrates especially at low hydrogen coverage, while the effects of the Au and graphene substrates on the HER activity are insignificant. The improvement is caused by the charge redistribution in the Mo 2 C layer on the substrate, and therefore the HER activity becomes high for any hydrogen coverage on the Ag and Cu substrates. Our results suggest that, in two-dimensional electrocatalysis, the substrate has a degree of freedom to tune the catalytic activity.