Crystallographic surface-resolved examination of protein-ZnO interactions can greatly enhance the fundamental understanding of protein adsorption on these technologically important solid surfaces which, in turn, will be tremendously valuable for the emerging applications of ZnO-based biomaterials and biosensors. We examine experimentally and via computer simulations the intriguing differences in the adsorption preferences and binding behavior of whole immunoglobulin G (IgG) proteins to various, low-index ZnO crystal surfaces at the individual biomolecule level. By performing direct atomic force microscopy imaging, we determine that IgG predominantly binds to the ZnO plane of (10 (1) over bar0) relative to the other three low-index planes of (0001), (000 (1) over bar), and (11 (2) over bar0). This phenomenon is highly unusual, particularly considering the fact that the average binding energy of amino acids (AAs) on the ZnO (0001) facet is higher than that on the (10 (1) over bar0) plane. In conjunction with combined Monte Carlo molecular dynamics simulations, we further explain the possible origins of our unusual experimental findings with critical factors such as the specific spatial locations of strongly binding AAs in the protein and their spatial distributions on the exterior surface of the protein.