Statistical analyses have been employed to develop analytical expressions for the surface coverage of chemically heterogeneous molecules adsorbed with extended-chain conformations onto chemically heterogeneous surfaces such that the single-chain adsorption enthalpy is minimized. Lateral interactions are neglected and a sufficient number of randomly distributed adsorption sites are included on both substrate and adsorbate such that site interactions are assumed to be nonoverlapping but otherwise independent. Good agreement is observed between the theoretical and experimentally determined surface fraction of a cationic polyacrylamide adsorbed from aqueous solution onto both a Nafion(R) ionomer membrane and numerous nonionic polymeric substrates. The more unique theoretical predictions for such enthalpy-driven adsorption processes are discussed.