Statistically clustering air pollution can provide evidence of underlying spatial processes responsible for intensifying the concentration of contaminants. It may also lead to the identification of hotspots. The patterns can then be targeted to manage the concentration level of pollutants. In this regard, employing spatial autocorrelation indices as important tools is inevitable. In this study, general and local indices of Moran's I and Getis-Ord statistics were assessed in their representation of the structural characteristics of carbon monoxide (CO) and fine particulate matter (PM 2.5 ) polluted areas in Tehran, Iran, which is one of the most polluted cities in the world. For this purpose, a grid (200 m × 200 m) was applied across the city, and the inverse distance weighted (IDW) interpolation method was used to allocate a value to each pixel. To compare the methods of detecting clusters meaningfully and quantitatively, the pollution cleanliness index (PCI) was established. The results ascertained a high clustering level of the pollutants in the study area (with 99% confidence level). PM 2.5 clusters separated the city into northern and southern parts, as most of the cold spots were situated in the north half and the hotspots were in the south. However, the CO hotspots also covered an area from the northeast to southwest of the city and the cold spots were spread over the rest of the city. The Getis-Ord's PCI suggested a more polluted air quality than the Moran's I PCI. The study provides a feasible methodology for urban planners and decision makers to effectively investigate and govern contaminated sites with the aim of reducing the harmful effects of air pollution on public health and the environment.