Industrialization, anthropogenic activities, the exhaust of vehicles and exponential population growth have a significant impact on the outdoor air quality of megacities across the world. Karachi is one of the largest cities in Pakistan, South Asia. The dense population, rapid economic growth and unplanned industrial activities have improved the socioeconomic status but also deteriorated the air quality of Karachi. The severe increase in air pollution has become a threat to the local population in terms of their health issues, quality of life and environment. Therefore, it is essential to quantify and monitor the spatiotemporal variation in outdoor air quality parameters. The current study aims to monitor the air quality in four major industrial zones of Karachi for three years (2020–2022). The field data was collected during the periods of post-monsoon and pre-monsoon using the HAZ-SCANNER (HIM-6000) apparatus, which measured outdoor air pollutants such as carbon monoxide (CO), nitrogen oxides (NO2), sulfur dioxide (SO2) and particulate matter (PM10, PM2.5 and TSPM). The data from 24 stations was analyzed using statistical analysis tools to estimate the parameters and Arc GIS to map the spatial variation of each parameter. The result shows that the concentration of particulate matter (TSPM, PM2.5 and PM10), SO2, NO2 and CO values at sampling sites are moderate in the post-monsoon season as compared to the pre-monsoon season due to cyclical monsoon effects and exceed the environmental quality standards. It was also noted that the North Karachi industrial area is at lower risk due to the small-scale industry. The higher levels of air pollutants have numerous health implications and may cause chronic infections. The air pollutant has a severe impact on plant growth and soil. Therefore, it is important to implement local environmental standards regarding outdoor air pollutants to mitigate the adverse impact on human health and economic activities.