We employed the density functional theory to investigate the interaction of H2O with Zn2GeO4 surfaces, considering both perfect and defective surfaces. The results revealed that the interaction of H2O with Zn2GeO4 surfaces was dependent on the structure of the latter. For perfect surfaces, H2O adsorbed at the Ge3c···O2c site of a (010) surface could spontaneously dissociate into an H atom and an OH group, whereas H2O tended to adsorb at the O2c-M3c-O3c site of a (001) surface by molecular adsorption. The presence of oxygen defects was found to strongly promote H2O dissociation on the (010) surface. Analysis of the surface electronic structure showed a large density of Ge states at the top of the valence band for both perfect and defective (010) surfaces, which is an important factor affecting H2O dissociation. In contrast, perfect and defective (001) surfaces with surface Ge states buried inside the valence band were significantly less reactive, and H2O was adsorbed on these surfaces in the molecular form. This information about the adsorbate geometries, catalytic activity of various surface sites, specific electronic structure of surface Ge atoms, and their relevance to surface structure will be useful for the future design of the Zn2GeO4 photocatalyst, as well as for the atomistic-level understanding of other structure-sensitive reactions.