The imbalance between the population, transportation, and construction is an important factor affecting coordinated regional development in China. Using transportation land area and population data from 2010, 2015, and 2020 in 121 counties (cities and districts) of Guangdong Province, this study analyzes the spatiotemporal changes in transportation land and population structure. It explores the relationship between transportation land and population size changes using exploratory spatial data analysis (ESDA) and decoupling models. Research suggests the following: (1) From 2010 to 2020, the per capita transportation land in various districts and counties of Guangdong Province showed a hierarchical structure of “low center and high periphery”. Conversely, the proportion of transportation land to construction land displayed a “high center and low periphery” characteristic. (2) During the same period, the total amount of transportation land in the peripheral areas of the Pearl River Delta was higher than that in the PRD (the Pearl River Delta) and the gap widened each year. Meanwhile, the proportion of transportation land to construction land in the peripheral areas of the Pearl River Delta was consistently higher than that in the PRD. (3) From 2010 to 2015, the relationship between population growth and transportation land in Guangdong Province showed a hierarchical pattern, while from 2015 to 2020, the pattern became more complex, and regional imbalance intensified. The decoupling results of PRD showed weak decoupling and expanding negative decoupling from 2010 to 2020. The peripheral areas of the Pearl River Delta are characterized by strong negative decoupling and expanding negative decoupling. Research has shown that although Guangdong Province is one of the most developed provinces in China, the mismatch between transportation land and population size in economically underdeveloped areas has become increasingly severe, with changes in the provincial population distribution pattern. The decoupling phenomenon between the transportation land and population is very obvious, and the policy of achieving regional balanced development through transportation infrastructure construction needs to be reviewed.