Increased industrialization and aging infrastructure have resulted in leaks of hazardous chemicals, such as CO. Leak modeling is crucial to developing emergency response strategies. Therefore, we simulated the time to criticality (TTC), which is the time to reach the threshold limit for occupational exposure, of a CO leak. The basis of the study is a fire dynamics simulator, a computational fluid dynamics model that was used to investigate the movement of CO in various scenarios, including using different building layouts and areas, temperatures, and leak diameters. Multiple regression analysis was performed to obtain regression equations for the TTC as a function of the independent variables. Ultimately, we found that the type of dispersion varies with respect to the temperature-dependent density of CO, and, among the independent variables, the leak diameter had the strongest effect on the TTC. The regression equations with logarithmic conversion were validated and found to have higher accuracy than those without logarithmic conversion. The findings provide useful information for developing emergency response plans regarding leak size in the case of hazardous chemical leakage. However, empirical studies of different gas types and leakage scenarios are required.