The main function zone (MFZ) is the major strategy of China’s economic development and ecological environment protection. Clarifying the logical relationship between “MFZ strategy” and “territorial spatial layout” is vital to construct regional economic layout and territorial spatial supporting system of high-quality development. However, few studies have revealed the evolution process and formation mechanism of the production-living-ecological space (PLES) structure of China’s MFZ over a long period of time. To bridge the gap, based on the land use dataset in China from 1980 to 2020, this study analyzed the evolution patterns of PLES in China’s MFZs using multiple methods and measured the formation mechanism of PLES in different types of MFZs with the GeoDetector model. Results showed that the spatial structure of China’s national territory has evolved drastically in the past 40 years, showing significant horizontal regional differentiation and vertical gradient differentiation. Ecological space has been continuously decreasing, while production space and living space have been continuously increasing, and the evolution of PLES varied significantly in different MFZs. During the study period, the gravity center of PLES in China all moved westward. The spatial distribution pattern of production space and living space was from northeast to southwest, and the ecological space was from east to west. The evolution of China’s territorial spatial structure was subject to the combined effects of natural and socio-economic factors, exhibiting significant differences in different MFZs. Land use intensity had the most prominent influence on the formation of PLES, followed by elevation. The influences of different factors on PLES structure were strengthened mainly through two types of nonlinear enhancement and dual-factor enhancement. This study can provide scientific support for the optimal management and high-quality development of territorial space in China.