Controlling the morphology of the as-synthesized nanostructures is usually challenging, and there lacks of a general theoretical guidance in experimental approach. In this study, a novel way of optimizing the aspect ratio of hydrothermally grown ZnO nanowire (NW) arrays is presented by utilizing a systematic statistical design and analysis method. In this work, we use pick-the-winner rule and one-pair-at-a-time main effect analysis to sequentially design the experiments and identify optimal reaction settings. By controlling the hydrothermal reaction parameters (reaction temperature, time, precursor concentration, and capping agent), we improved the aspect ratio of ZnO NWs from around 10 to nearly 23. The effect of noise on the experimental results was identified and successfully reduced, and the statistical design and analysis methods were very effective in reducing the number of experiments performed and in identifying the optimal experimental settings. In addition, the antireflection spectrum of the as-synthesized ZnO NWs clearly shows that higher aspect ratio of the ZnO NW arrays leads to about 30% stronger suppression in the UV-vis range emission. This shows great potential applications as antireflective coating layers in photovoltaic devices.