The photocatalytic activity of photocatalysts is often influenced by their particle morphology, dimension, size, exposed facets, porosity, etc. This work aims at gaining insights into the influence of the particle morphology of ZnO nanostructures on their photocatalytic activity. Under hydrothermal conditions, the Zn(NO3)2∙6 H2O:KOH (Zn:KOH) ratio is changed to 1:2, 1:8, and 1:12 to modulate the morphology of ZnO nanostructures. Particularly, the ZnO nanostructures with a nanostar-like morphology, synthesized at the Zn:KOH ratio of 1:8, exhibit the highest photocatalytic activity in comparison to ZnO nanoparticles and nanorods synthesized at the Zn:KOH ratios of 1:2 and 1:12, respectively. The enhanced photocatalytic activity for the degradation of methylene blue (MB) of ZnO nanostructures with a nanostar-like morphology is due to the presence of a large number of oxygen vacancy-related defects, which are preferably formed on the (1 0 1) facet of ZnO. The results from X-ray diffraction and photoluminescence spectroscopy analyses confirm it. Further, molecular dynamics (MD) simulation is involved to explore the interaction of oxygen atoms (as a representative of hydroxyl radical) with methylene blue molecules to understand the mechanism of enhanced MB degradation at the atomic level. The results of the computational study indicate the formation of hydroxyl radicals and the cleavage and the formation of some bonds in the side and central aromatic rings of MB molecules, which ultimately leads to the degradation of MB. Our findings reveal that it is important to control the morphology and facets of nanostructures for achieving high efficiency in the photocatalytic processes to be applied in practical application.