The antibacterial responses of zinc oxide (ZnO) structures against Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes were investigated. Two ZnO powder samples, one with rod-like (ZnO-1) and the other with plate-like (ZnO-2) structures, were characterized for their morphological, structural, and optical properties. The rods were 30–120nm in diameter, and the plates were 40–100nm thick. XRD results revealed the wurtzite crystallinity of ZnO with average crystallite sizes of 33.72 (ZnO-1) and 39.25 (ZnO-2)nm. ZnO-2 possessed a relatively higher green photoluminescence than that of ZnO-1, suggesting a relatively higher amount of oxygen vacancies in ZnO-2 structures. Optical density measurements showed that both ZnO samples inhibited the growth of S. aureus, P. aeruginosa, and S. pyogenes by 29–98% after 24h of treatment. The most dramatic growth inhibition was observed in S. pyogenes with 96% and 98% inhibition for ZnO-1 and ZnO-2, respectively, leading to a probable bactericidal phenomenon. The toxicological effect on S. pyogenes was probably due to the absence of catalase, making the bacteria vulnerable to the harmful reactive oxygen species (ROS) released by ZnO. ZnO-1 induced higher inhibition toward S. aureus and P. aeruginosa than that of ZnO-2 because of the smaller particle size of rod structures compared to plate and slab structures. The adhesion of ZnO particles on the membrane of bacteria could be the underlying cause of zinc toxicity effect towards the bacteria. ZnO-1 possessed larger surface area and provided higher amount of zinc atom, thereby inducing higher level of toxicity toward the bacteria. Two possible mechanisms were proposed to explain the inhibition of bacteria, namely, ROS toxicity toward cellular constituents and interaction of zinc with bacteria membrane through adhesion of ZnO particle. Several ZnO morphological-antibacterial correlations were presented in this work.