Regional high-quality coordination plays a crucial role in promoting high-quality national development. Guangdong province is a trailblazer in China’s reform and opening-up policies and high-quality development. This study analyzes the high-quality development of the economic, social, and ecological environments from 2010 to 2019 in Guangdong with the entropy weight TOPSIS model. Meanwhile, the coupling coordination degree model is used to investigate the spatial-temporal pattern of the coupling and coordinated development of the three-dimensional system in 21 prefecture-level cities. The results show that the high-quality development index of Guangdong increased from 0.32 to 0.39, a 21.9% increase during 2010–2019. The Pearl River Delta had the highest value of the high-quality development index, whereas Western Guangdong had the lowest level in 2019. Guangzhou, Shenzhen, Zhuhai, and Dongguan are the core cities in the high-quality development of Guangdong, with the index decreasing from the Pearl River Delta estuary cities to the province’s edge. We also found that the coupling degree and coupling coordination of high-quality development of the three-dimensional system grew slowly during the study period. Half of the cities in Guangdong entered the stage of benign coupling. Except for Zhaoqing, all cities in the Pearl River Delta have a high coupling coordination degree of high-quality development of the three-dimensional system. This study provides valuable references for the high-quality, coordinated development of Guangdong province and some policy suggestions for other regions.