Thermal management is critically important to maintain the performance and prolong the lifetime of a lithium-ion (Li-ion) battery. In this paper, a two-dimensional and transient model has been developed for the thermal management of a 20-flat-plate-battery stack, followed by comprehensive numerical simulations to study the influences of ambient temperature, Reynolds number, and discharge rate on the temperature distribution in the stack with different cooling materials. The simulation results indicate that liquid cooling is generally more effective in reducing temperature compared to phase-change material, while the latter can lead to more homogeneous temperature distribution. Fast and deep discharge should be avoided, which generally yields high temperature beyond the acceptable range regardless of cooling materials. At low or even subzero ambient temperatures, air cooling is preferred over liquid cooling because heat needs to be retained rather than removed. Such difference becomes small when the ambient temperature increases to a mild level. The effects of Reynolds number are apparent in liquid cooling but negligible in air cooling. Choosing appropriate cooling material and strategy is particularly important in low ambient temperature and fast discharge cases. These findings improve the understanding of battery stack thermal behaviors and provide the general guidelines for thermal management system. The present model can also be used in developing control system to optimize battery stack thermal behaviors.