Zinc−bromine redox flow battery (ZBFB) is one of the most promising candidates for large-scale energy storage due to its high energy density, low cost, and long cycle life. However, numerical simulation studies on ZBFB are limited. The effects of operational parameters on battery performance and battery design strategy remain unclear. Herein, a 2D transient model of ZBFB is developed to reveal the effects of electrolyte flow rate, electrode thickness, and electrode porosity on battery performance. The results show that higher positive electrolyte flow rates can improve battery performance; however, increasing electrode thickness or porosity causes a larger overpotential, thus deteriorating battery performance. On the basis of these findings, a genetic algorithm was performed to optimize the batter performance considering all the operational parameters. It is found that the battery energy efficiency can reach 79.42% at a current density of 20 mA cm−2. This work is helpful to understand the energy storage characteristics and high-performance design of ZBFB operating at various conditions.