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The economic and social development evaluation system with the Gross Domestic Product (GDP) as the leading indicator is no longer applicable to the current social progress in China. It is essential to carry out an assessment of the Gross Ecosystem Product (GEP) to integrate ecological benefits into the economic and social evaluation system and promote sustainable socio-economic development. This study took Guangxi, an important province in South China, as the study area. We used four periods of land use and land cover data (LULC), meteorological data, soil data and yearbook statistics to construct a GEP assessment framework based on geographic information system (GIS) and remote sensing (RS) technologies. We accounted for the provisioning services, regulating services, and tourism services provided by Guangxi in 2005, 2010, 2015, and 2020 and analyzed the region’s and municipalities’ spatial–temporal pattern characteristics and trends of change in GEP. In addition, this study also discusses the relationship between GEP and GDP. The results showed that many important products and services provided by natural ecosystems in Guangxi had enormous economic benefits. GEP had increased from CNY 15,657.37 billion in 2005 to CNY 36,677.04 billion in 2020, and the distribution of GEP showed obvious spatial heterogeneity. The value of ecosystem regulation services was about 65–89% of GEP, which is the main component of GEP. From 2005 to 2020, natural ecosystem protection and socio-economic development have achieved coordinated development in Guangxi. GEP and GDP showed upward trends in general. Although Guangxi is relatively backward in terms of economic development, the scientific quantification of the unrealized value of the services provided by the ecosystem through GEP accounting makes it possible to transform ecological advantages into economic advantages. It could help the local government and people to re-recognize the value of ecological resources and realize the beautiful vision of lucid waters and lush mountains as invaluable assets.