Vertical shaft natural ventilation is a common smoke exhaust method in highway tunnel fires. This study investigated the vertical shaft natural smoke exhaust work in highway tunnel fires with the effect of multiple factors through numerical simulation. Using the analysis of the flow field of smoke in nearby areas of the vertical shaft and the quantitative calculation of the gas exhausted through the vertical shaft, considering the impact of shaft division and board height, an optimal vertical shaft arrangement was proposed, and the working conditions of this arrangement in low-pressure environments were discussed. The results show that dividing a single large vertical shaft into multiple small vertical shafts and appropriately adjusting the board height can reduce the incidence of vertical shaft plug holes and significantly enhance the vertical shaft smoke exhaust performance. Meanwhile, the board-coupled shaft (BCS) has excellent working ability in low-pressure environments, and when pressure drops, smoke exhaust efficiency will improve. This research offers a foundation and reference value for improving the vertical shaft smoke exhaust system in highway tunnels.