The reactive metal-support interaction in the Cu-In₂O₃ system and its implications on the CO₂ selectivity in methanol steam reforming (MSR) have been assessed using nanosized Cu particles on a powdered cubic In₂O₃ support. Reduction in hydrogen at 300 °C resulted in the formation of metallic Cu particles on In₂O₃. This system already represents a highly CO₂-selective MSR catalyst with ~93% selectivity, but only 56% methanol conversion and a maximum H₂ formation rate of 1.3 µmol g_Cu ^-1 s^-1. After reduction at 400 °C, the system enters an In₂O₃-supported intermetallic compound state with Cu₂In as the majority phase. Cu₂In exhibits markedly different self-activating properties at equally pronounced CO₂ selectivities between 92% and 94%. A methanol conversion improvement from roughly 64% to 84% accompanied by an increase in the maximum hydrogen formation rate from 1.8 to 3.8 µmol g_Cu ^-1 s^-1 has been observed from the first to the fourth consecutive runs. The presented results directly show the prospective properties of a new class of Cu-based intermetallic materials, beneficially combining the MSR properties of the catalyst's constituents Cu and In₂O₃. In essence, the results also open up the pathway to in-depth development of potentially CO₂-selective bulk intermetallic Cu-In compounds with well-defined stoichiometry in MSR.