Electrochemical reduction of carbon dioxide (CO2RR) is promoted by ionic liquid (IL) co-catalysts, and several mechanisms have been proposed to explain their role. Due to the complexity of the CO2RR and the limited number of active IL co-catalysts, a consensus on the precise role of ILs has not been reached, and it is not possible to improve their activity in a rational way. Herein, we describe guanidinium (Gua) ILs that act as co-catalysts for the CO2RR when employed in non-aqueous electrolytes. The peripheral substituents of the Gua cation were systematically modified allowing the IL co-catalytic properties to be fine-tuned, and on the basis of the observed substitution effects, charge delocalization and availability were shown to be the critical descriptors determining co-catalytic activity. These descriptors can be used to rationalize activity trends for other classes of IL co-catalysts.