The aim of this study was to evaluate the transport phenomena of smoke flow and vertical temperature distribution in a 21-story stairwell with multiple fire locations and openings. A large eddy simulation (LES) method was used to model the smoke flow in a stairwell model with a set of simulation parameters, wherein the fire heat release rate (HRR) and fire location were varied. Based on the results, a wall attachment effect was found in three-dimensional figures. Moreover, with an increase in the fire HRR, the effects were more pronounced. The simulation results verified that the vertical temperature distribution is an index model with a natural logarithm, where the pre-finger factor and attenuation coefficient increase considerably in accordance with an increase in the fire HRR. Moreover, there was a decrease in the maximum temperature (Tm) with an increase in the fire location factor (h*) due to the upward thermal smoke. Moreover, heat mainly accumulates in the area above a fire source. However, h* has a slight influence on the time required to reach Tm within the range of 53–64 s. Furthermore, the direction of the airflow at each side opening in the stairwell varied in accordance with the variation in the fire location changes, and a regular calculation was carried out.