Aim: This study was conducted to evaluate the effects of ambient concentrations of PM2.5 and PM10 on the health-related aspects including the total mortality, respiratory and cardiovascular diseases, and hospital admissions due to respiratory and cardiovascular diseases in Karaj, Alborz Province, Iran, during 2012–2016 using the AirQ2.2.3 software. The effects of meteorological parameters on the PM2.5 and PM10 levels were also investigated. Materials and Methods: Meteorological parameters, population, and the pollutant data were obtained from the Department of Environmental Protection, Karaj (Alborz, Iran). Statistical analysis was performed using the SPSS 24 software to study the relationship between the PM2.5 and PM10 concentrations and the meteorological parameters. Results: Our results showed a direct relationship between the PM10 concentration and the temperature (r = 0.34, P < 0.018) and relative humidity (r = 0.37, P < 0.5). However, there was a negative relationship between the PM10 concentration with wind speed (r < −0.328, P < 0.014) and precipitation (r < −0.179, P < 0.327). Similarly, there was a direct relationship between the PM2.5 concentration and the temperature (r = 0.41, P < 0.014) and relative humidity (r = 0.37, P < 0.05). On the other hand, a negative relationship was observed between the PM2.5 concentration with wind speed (r < −0.138, P < 0.010) and precipitation (r < −0.12, P < 0.201). The total number of death, death due to cardiovascular and respiratory diseases, and hospital admissions due to cardiovascular and respiratory diseases were equal to 1619, 1096, 306, and 4822, respectively. Conclusions: The results of this study showed that the concentrations of PM2.5 and PM10 should be reduced through applying the management strategies to improve the health of the residents in Karaj city.