This benchmark study documents a combined computational and experimental investigation into the binding of three commercial dithio collector ligands used in industrial froth flotation processes to separate high-value minerals from lower-value materials. First-principles condensed-matter simulations showed that ethyl xanthate, N,N-diethyl dithiocarbamate, and diisobutyl dithiophospinate anions all bind least strongly to the  Miller index plane of the platinum-containing mineral sperrylite, followed by the  MI surface of the mixed nickel/iron sulfide mineral pentlandite, whereas all ligands showed the strongest binding affinity to the  MI surface model of pure platinum. Calculations also support experimental observations that neutral ethyl xanthogen disulfide formed upon oxidation of ethyl xanthate binds much more weakly than the monomer. A monolayer of water molecules would easily be displaced from all surfaces by any of the collector ligands. The hydroxide anion was found to have binding energies with magnitudes comparable to those of the collector ligands on all surfaces. Cyclic voltammetry measurements performed on working electrodes constructed from sperrylite, pentlandite, and platinum permitted measurement of the mixed oxidation potential associated with the surface dimerization reaction for all three collector ligands, although the data obtained for diisobutyl dithiophospinate were less clear-cut than those obtained for the other ligands. Comparison of the relative ordering of the mixed potentials for the three ligands gave a favorable match with the predicted outcome of binding energy strengths obtained from the modeling study. This study demonstrates that first-principles simulations can be used to predict the binding energies of collector ligands to mineral and metallic surfaces.