Signal enhancement technology (sub-pixel interpolation) is used to obtain SO2 column concentrations for Guangdong Province in China from 2005 to 2016. The high resolution (2 km × 2 km) data used was obtained via a remote sensing satellite (Ozone Monitoring Instrument) and verified by comparing it with average annual SO2 data recorded in ground monitoring stations. The correlation was found to be up to 0.95. Moreover, the data was cross-correlated with national and regional inventories of pollution sources. The results show that the regional characteristics of the spatial distribution obtained are consistent and the detailed characteristics are highly coincidental. Based on this, the new and detailed spatiotemporal variation was analyzed and the effect of emission reduction in urban agglomerations on the SO2 concentration in the Pearl River Delta (PRD) region of China investigated. The results demonstrate that the distribution of SO2 pollution in the PRD has been transformed over the period studied. In the early stages, it had a traditional high-concentration type of distribution (with agglomeration areas like Guangzhou and Foshan as high-concentration pollution centers) and this has changed to the currently-observed low-concentration decentralized type of distribution (mainly distributed along administrative boundaries). In the last 10 years, significant SO2 emission reduction has occurred in prefecture-level cities, e.g., Foshan, Zhongshan, and Guangzhou (with emission-reduction amplitudes of 71%, 65%, and 57%, respectively). Foshan and Zhongshan are the top two prefecture-level cities in the PRD region in terms of significant reduction in rate of SO2 contribution. The SO2 contribution rate fell from 17% to 13% in Foshan and from 16% to 10% in Zhongshan. However, the relative contribution rates in Zhaoqing and Huizhou increased from 7% to 11% and from 6% to 10%, respectively. The size of the emission reduction and changes in SO2 contribution rates in the prefecture-level cities in the PRD region show that the government’s efforts to improve air quality have had a significant effect.