Cooperative interactions in ligand binding processes are important considerations when developing functional materials and controlling catalytic reactions. Here we report on ligand binding to metal porphyrins on HOPG at the solution-solid interface. Using scanning tunneling microscopy (STM) and density functional theory (DFT) we show the existence of cooperativity in ligand binding. Experimental measurements of the distribution of ligand-bound porphyrins from STM images are combined with energetics, and charge distributions from DFT calculations in order to better understand cooperative behavior at the single-molecule level. The heats of wetting of surfaces and reagents are considered in the calculations.