The surface properties of zinc oxide powders prepared using mechanical activation, electron beam irradiation, and vacuum annealing, as well using combinations of these types of treatments, were studied using X-ray photoelectron spectroscopy. The structure of the obtained materials was studied by an X-ray diffraction technique and by scanning electron microscopy. We found that over five hours of grinding in an attritor, the size of nanocrystals decreases from 37 to 21 nm, and microdeformations increase from 0.3% to 0.6%. It was also found that a five-hour grinding treatment promoted formation of vacancies in the zinc sublattice at the surface and diffusion of Zn²⁺ cations into the bulk of the material. Irradiation of commercial zinc oxide powders with an electron beam with an energy of 0.9 MeV and a dose of 1 MGy induced breaking of Zn–O bonds, diffusion of interstitial zinc ions into the bulk, and oxygen atom escape from regular positions into the gas phase. A combined treatment of five hours of grinding and electron beam irradiation promoted accumulation of interstitial zinc ions at the surface of the material. Annealing of both initial and mechanically activated ZnO powders at temperatures up to 400 °C did not lead to a significant change in the properties of the samples. Upon exceeding the 400 °C annealing temperature the X-ray photoelectron spectra show almost identical atomic composition of the two types of materials, which is related to diffusion of interstitial zinc ions from the bulk of the material to the surface.