After the reform and opening up of China began in 1978, Guangdong province made great achievements in economic development and urbanization, achieving international significance with its “Guangdong development model.” In recent years, accompanied by changes in the external environment and internal conditions, a new phenomenon, named urban shrinkage, has occurred during the process of rapid urbanization, with such features as economic decline, population outflows, and vacant dwellings, in complete contrast to the traditional development path. Given this phenomenon, this paper dynamically observes the changes to the number of permanent residents and the registered population of cities above county level from 2000 to 2016. By classifying three typologies of urban population shrinkage-continuous shrinkage, episodic shrinkage, and no shrinkage-we analyze the time trajectory and spatial distribution of urban population shrinkage. In addition, we discuss the factors influencing the shrinkage of cities in Guangdong province by using a regression model to explore the effects of potential determinants (manufacturing sector, service sector, fixed-asset investment scale, public services levels in cities, average income of industrial workers, and local government financial status) on urban population shrinkage. The study had several findings. First, general growth accompanied by local shrinkage is the main characteristic of urban population change in Guangdong. The change in permanent population shrinkage is characterized by fluctuations and short-termism, and its trajectory is V-shaped, while the household registration population change is relatively stable. Second, in spatial terms, urban population shrinkage presents a distribution pattern of “core growing-edge shrinking,” with cities showing continuous or episodic shrinkage mainly concentrated in the eastern and northern parts of Guangdong. In contrast to the zonal distribution of resident population shrinkage, household registration population shrinkage is mainly distributed scattered, with four counties in Qingyuan city being typical of edge-shrinking cities in Guangdong. Third, urban population shrinkage no longer follows a simple linear process at the provincial level but involves a combination of multidimensional and multifactorial motivations, including economic, institutional, social, and demographic. Industrial economic decline, regional developmental differences, local financial shortages, and local population outflows are the main factors influencing urban population shrinkage in Guangdong province. Our study offers a comprehensive method, using different typologies, for understanding urban shrinkage in its spatiotemporal evolution and provides new research evidence for determining the influences on shrinking cities in areas of rapid urbanization.