Owing to their large specific energy density and eco-friendliness, zinc-air batteries (ZABs) are seen to be potential large-scale rechargeable batteries. In recent years, numerous attempts have been made to develop zinc-air flow batteries (ZAFBs) with the premise that a flowing electrolyte can alleviate the shortcomings of zinc electrodes. Herein, the effects of electrolyte flow rate, current density, initial ZnO concentration, and electrolyte temperature on the performance and efficiency of a ZAFB are systematically explored. In addition, the paper discusses the morphological evolution of a zinc electrode with respect to different levels of parameters as well as gravity. Optimal parameters are determined by employing a combination of orthogonal array (OA) sampling and response surface methodology. Results demonstrate that a two-factor interaction regression model can effectively predict actual results with quite an acceptable accuracy. Applying optimal conditions, the battery obtains 99.27 % charge efficiency, 97.65 % discharge efficiency, 73.52 % overall round-trip efficiency, and charge and discharge overpotentials as low as 0.36 V and 0.09 V, respectively. The optimized ZAFB is able to attain superior performance with enhanced round-trip efficiency, making it appropriate for large-scale development.