ZnO spherical powder with hierarchical structure was synthesized from zinc acetate anhydride and hexamethylenetetramine in a solvent of water and ethylene glycol (EG), and its time evolution was investigated by microscopic and isotope tracer studies. Initially, spherical ZnO particles made of nanocrystallites were precipitated. From the early growth stage, crystallites were radially aligned along the c-axis. With aging, the nanoparticles transformed into hexagonal prism-like particles with pyramidal tops, which showed clear radial alignment. Subsequently, the ZnO spheres became cracked and broke into wedge-shaped pieces of the pyramid-like particles. The microscopic studies suggested that the spherical particles grew through oriented attachment of small particles during the early growth stage, while Ostwald ripening through dissolution–recrystallization changed the component particles to a pyramidal shape in the later stage. In order to investigate the growth process, we attempted a novel isotope tracer study, where H218O was used for the solvent and the distribution of 18O in the spherical particles was analyzed by a secondary ion mass spectrometer. The concentric 18O distribution in the ZnO spherical powder aided the mechanism of continuous concentric-oriented attachment of nanoparticles to form spherical ZnO particles. The difference in the 18O distribution before and after transformation into the pyramid shape was small, which implies that this change was a local reaction. The oxygen isotope tracer study in water–EG solvent was proven effective in determining the history of the particles and the development of their inner structures.