Guangxi Zhuang Autonomous Region, located in the southwest of China, has rapidly developed since the late 2000s. Similar to other regions, economic development has been accompanied by environmental problems, especially air pollution, which can adversely affect the health of residents in the area. In this study, we estimated the negative health effects of three major ambient pollutants, Particulate Matter with a diameter of 10 μm or less (PM10), Sulfur Dioxide (SO2) and Nitrogen Dioxide (NO2) in Guangxi from 2011 to 2016 using a log-linear exposure–response function. We monetarized the economic loss using the value of statistical life (VSL) and the cost of illness (COI) methods. The results show that the total possible short-term all-cause mortality values due to PM10, SO2, and NO2 were 28,396, with the confidence intervals from 14,664 to 42,014 (14,664–42,014), 24,618 (15,480–33,371), and 46,365 (31,158–61,423), respectively. The mortality from the three pollutants was 48,098 (19,972–75,973). The economic loss of the health burden from the three pollutants was 40,555 (24,172–57,585), which was 2.86% (1.70–4.06%) of the regional gross domestic product. The result of the comparative analysis among different cities showed that urbanization, industrialization, and residents’ income are important factors in air-pollution-caused health damage and subsequent economic loss. We conclude that the health burden caused by ambient pollutants in developing regions, accompanied by its rapid socio-economic growth, is significant and tighter regulation is needed in the future to alleviate air pollution and mitigate the related health damage.