Residential energy consumption (REC) is now the second largest energy sector in China. However, decoupling analysis of REC has not received enough attention. Here, we explore the decoupling relationship between REC and economic growth in urban and rural Guangdong from 2000 to 2017. First, we use the Tapio decoupling model to study the decoupling state. Then, key drivers affecting the decoupling were explored by combining the Tapio decoupling model with the Log-mean Divisa Index (LMDI) method. Finally, the decoupling efforts were evaluated by using the decoupling efforts model. The main results are as follows: (1) The decoupling state in urban regions was better than that in rural regions. Urban regions experienced weak decoupling (WD) in most years during 2000−2017, while expansive negative decoupling (END) mostly was seen in rural regions. (2) The per capita income effect was the most important driver inhibiting decoupling in Guangdong urban and rural regions. The energy intensity effect was the biggest driver promoting decoupling in urban Guangdong, followed by the family size effect. In contrast, the family size effect exerted the dominant influence on accelerating the decoupling in rural Guangdong. Overall, the household effect inhibited decoupling in urban regions, but promoted decoupling in rural regions. (3) The decoupling efforts results suggest that the energy efficiency improvement played a major role in the decoupling efforts of urban Guangdong, while the decrease of family size in rural Guangdong was the leading contributor to the decoupling efforts.