Abstract In the early 2000s, the Pearl River Delta (PRD) became one of the earliest regions in China to implement a stringent control policy on air pollution emission. In particular, during the 11th Five Year Plan (FYP) and 12th FYP (i.e., 2006–2015), the emission control measures were executed intensively and efficiently under the supervision of law enforcement authorities. These measures helped substantially reduce the fine particulate matter (PM2.5) concentration over this region. Hence, it is now important to determine how the decrease in PM2.5 concentration influenced the exposure condition and health burdens in the PRD region during 2006–2015. In this study, the exposure and mortality apportionment of PM2.5 under both 2006 and 2015 emission scenarios were investigated. The simulated population-weighted PM2.5 concentration was found to be lower under the 2015 emission scenario compared with that under the 2006 scenario. The average reductions in simulated PM2.5 exposure concentrations (population-weighted average) for Guangzhou, Dongguan, Foshan, and Shenzhen were 32.7, 27.0, 25.3, and 24.1 μg/m3, respectively. After excluding the meteorological variations, a difference of approximately 16,400 (95% CI: 9,100, 22,800) in the number of simulated premature deaths was obtained after the 10-year efforts for emission control and industrial restructuring. Among the five major anthropogenic emissions (mobile, area, power plant, marine vessel, and industrial point emissions), the control of mobile emissions was found to be the most relevant to the estimated health benefits. The calculated economic benefits from controlling mobile emissions reached 30,300 (21,600, 37,100) million USD in 2015. In contrast, the mortality related to area emissions turned out to be higher under the 2015 emission scenario. The difference between 2006 and 2015 meteorological scenarios could substantially influence the simulated exposure concentration in each month. However, the impact of the meteorological factors was found to be limited when the exposure concentrations of the 4 months were averaged. Further, 26,700 (18,500, 33,400) premature deaths difference was calculated after the PM2.5 concentration over the PRD region reached the Air Quality Guideline standard. Therefore, more efforts, including the control of area emissions and the enhancement of regional cooperation (e.g., reducing industrial emission consistently and systematically in southern China), are crucial further to reduce the PM2.5 concentrations in the PRD region and improve the living conditions for the residents.