To form nanopatterns with self-assembled block copolymers (BCPs), it is desirable to have through-film domains that are oriented perpendicular to the substrate. The domain orientation is determined by the interfacial interactions of the BCP domains with the substrate and with the free surface. Here, we use thin films of two different sets of BCPs with A-block-(B-random-C) architecture matched with a corresponding B-random-C copolymer nanocoating on the substrate to demonstrate two distinct wetting behaviors. The two sets of A-b-(B-r-C) BCPs are made by using thiol-epoxy click chemistry to functionalize polystyrene-block-poly(glycidyl methacrylate) with trifluoroethanethiol (TFET) and either 2-mercaptopyridine (2MP) or methyl thioglycolate (MTG). For each set of BCPs, the composition ratio of the two thiols in the BCP (φ1) is found that results in the two blocks of the modified BCP having equal surface energies (Δγair = 0). The corresponding B-r-C random copolymers were synthesized and used to modify the substrate, and the composition ratio (φ2) values that resulted in the two blocks of the BCP having equal interfacial energy with the substrate (Δγsub = 0) were determined with scanning electron microscopy. The correlation between each block's γsub value and the interaction parameter, χ, is employed to explain the different wetting behaviors of the two sets of BCPs. For the thiol pair 2MP and TFET, the values of φ1 and φ2 that lead to Δγair = 0 and Δγsub = 0, respectively, are significantly different. A similar difference was observed between the φ1 and φ2 values that lead to Δγair = 0 and Δγsub = 0 for the BCPs made with the thiol pair MTG and TFET. In the latter case, for Δγsub = 0 two windows of φ2 are identified, which can be explained by the thermodynamic interactions of the specific thiol pair and the A-b-(B-r-C) architecture.