Urban air quality is composed of a complex interaction of factors associated with anthropogenic emissions, atmospheric circulation, and geographic factors; also, most of the urban pollution presents aerosols and trace gases toxic to human health and responsible for damaged flora, fauna, and materials. The air quality system based on the state-of-the-art Weather Research and Forecasting model coupled with chemistry (WRF-Chem) has been configured and designed for Macedonia. An extensive set of experiments have been performed with different model settings to forecast simultaneously the weather and air pollution over Macedonia. For the present work, a numerical simulation of extreme pollution episode over the urban area in Skopje has been simulated using 1-km WRF-Chem model and a newly developed set of urban mobile emissions. The modeled results implied that the model is very sensitive to the initial meteorological conditions, grid spacing, and mobile emissions. The results are validated against available observations for meteorological fields and pollutant concentrations. While the model forecasts with coarser horizontal grid resolution well fit with the hourly values of some air quality monitoring stations, these experiments tend to underpredict the peak level of about 1250 μg/m3 evidenced at the air quality station “Karpos.” A WRF-Chem 5-km simulation shows increased PM10 concentrations with a peak value of about 1325 μg/m3 a few hours before the evidenced extreme concentration while 2.5-km grid run indicates the initial accumulation of air pollution with relatively high concentration with peak PM10 on 5 February 2017 at 0100 UTC. The 1-km model configuration well captures the PM10 distribution over Skopje valley and the location and timing of the maximum measured air pollution. The verification analysis indicates that the best performance in the sense of the correlation coefficient is achieved with the 5-km WRF-Chem v.3.91 forecast. Numerical simulations with coarser grid resolution show less confidence and lower CC. The results suggest that model initialization and initial data using a mobile source emission provide a better quantitative assessment of extreme air pollution in urban areas. Overall, the present case study shows that the WRF-Chem model has an acceptable performance for meteorological variables as well as PM10 concentration over Skopje. This study provides a general overview of WRF-Chem simulations and can serve as a reference for future air quality modeling studies.