Providing a quantitative understanding of the thermodynamics involved in molecular adsorption and self-assembly at a nanostructured carbon material is of fundamental importance and finds outstanding applications in the graphene era. Here, we study the effect of edge perchlorination of coronene, which is a prototypical polyaromatic hydrocarbon, on the binding affinity for the basal planes of graphite. First, by comparing the desorption barrier of hydrogenated versus perchlorinated coronene measured by temperature-programmed desorption, we quantify the enhancement of the strength of physisorption at the single-molecule level though chlorine substitution. Then, by a thermodynamic analysis of the corresponding monolayers based on force-field calculations and statistical mechanics, we show that perchlorination decreases the free energy of self-assembly, not only enthalpically (by enhancing the strength of surface binding), but also entropically (by decreasing the surface concentration). The functional advantage of a chemically modulated 2D self-assembly is demonstrated in the context of the molecule-assisted liquid-phase exfoliation of graphite into graphene.