Monodisperse wurtzite ZnS hollow spheres with diameters of about 200 nm and shells composed of nanoparticles have been successfully synthesized in high yield by a one-pot template-free hydrothermal route. The reaction duration, reactant species, and reaction temperature have been shown to play important roles in the formation of ZnS hollow spheres. X-ray diffraction, scanning and transmission electron microscopy, nitrogen adsorption/desorption, UV/Vis diffuse reflectance spectroscopy, and photoluminescence were used to characterize the products. The results show that all the prepared nanospheres have hexagonal wurtzite structures and exhibit good size uniformity and regularity. A mechanism for the formation of the ZnS hollow spherical structure by localized Ostwald ripening has been proposed based on experimental observations. In addition, studies of the photocatalytic properties of the ZnS hollow spheres by exposure to UV irradiation have demonstrated that they have potential photocatalytic applications. Hydroxyl radicals (*OH) were not detected on the surface of UV-illuminated ZnS by the photoluminescence technique, which suggests that *OH is not the dominant photo-oxidant and a photogenerated hole could instead directly participate in the photocatalytic reaction. The prepared ZnS hollow spheres are also of great interest for use in flat displays, sensors, lasers, catalysis, separation technology, biomedical engineering, and nanotechnology.