Air pollution and extreme heat have been responsible for more than a million deaths in China every year, especially in densely urbanized regions. While previous studies intensively evaluated air pollution episodes and extreme heat events, a limited number of studies comprehensively assessed atmospheric hot-and-polluted-episodes (HPE) - an episode with simultaneously high levels of air pollution and temperature - which have potential adverse synergic impacts on human health. This study focused on the Pearl River Delta (PRD) region of China due to its high temperature in summer and poor air quality throughout a year. We employed geostatistical downscaling to model meteorology at a spatial resolution of 1 km, and applied a machine learning algorithm (XGBoost) to estimate a high-resolution (1 km) daily concentration of particulate matter with an aerodynamic diameter ≤2.5 μm (PM(2.5)) and ozone (O(3)) for June to October over 20 years (2000-2019). Our results indicate an increasing trend (∼50%) in the frequency of HPE occurrence in the first decade (2000-2010). Conversely, the annual frequency of HPE occurrence reduced (16.7%), but its intensity increased during the second decade (2010-2019). The northern cities in the PRD region had higher levels of PM(2.5) and O(3) than their southern counterparts. During HPEs, regional daily PM(2.5) exceeded the World Health Organization (WHO) and Chinese guideline levels by 75% and 25%, respectively, while the O(3) exceeded the WHO O(3) standard by up to 69%. Overall, 567,063 (95% confidence interval (CI): 510,357-623,770) and 52,231 (95%CI: 26,116-78,346) excessive deaths were respectively attributable to exposure to PM(2.5) and O(3) in the PRD region. Our findings imply the necessity and urgency to formulate co-benefit policies to mitigate the region's air pollution and heat problems.