The impact of air pollution on human health is becoming increasingly severe, and economic losses are a significant impediment to economic and social development. This paper investigates the impact of air pollutants on the respiratory system and its action mechanism by using information on inpatients with respiratory diseases from two IIIA (highest) hospitals in Wuhan from 2015 to 2019, information on air pollutants, and meteorological data, as well as relevant demographic and economic data in China. This paper describes the specific conditions of air pollutant concentrations and respiratory diseases, quantifies the degree of correlation between the two, and then provides a more comprehensive assessment of the economic losses using descriptive statistical methods, the generalized additive model (GAM), cost of illness approach (COI), and scenario analysis. According to the findings, the economic losses caused by PM2.5, PM10, SO2, NO2, and CO exposure are USD 103.17 million, USD 70.54 million, USD 98.02 million, USD 40.35 million, and USD 142.38 million, for a total of USD 454.46 billion, or approximately 0.20% of Wuhan’s GDP in 2019. If the government tightens control of major air pollutants and meets the WHO-recommended criterion values, the annual evitable economic losses would be approximately USD 69.4 million or approximately 0.03% of Wuhan’s GDP in 2019. As a result, the relevant government departments must strengthen air pollution control to mitigate the impact of air pollution on population health and the associated economic losses.