Improving tourism’s ecological efficiency and facilitating harmony between tourism development and the ecological environment are profitable and conducive to sustainable development. In this study, we investigated the relationship between tourism’s eco-efficiency for sustainable tourism development and environmental protection by incorporating unexpected outputs to calculate tourism’s eco-efficiencies, analyzing the three-dimensional spatial variation and, finally, considering the effects of nine comprehensive factors on the extent of the spatial variation in tourism efficiencies: economic development, openness, social consumption, the digital economy, transportation infrastructure, government intervention, technological innovation, energy consumption, and passenger turnover. First, an unexpected slack-based measure model was applied to calculate the tourism ecological efficiencies of 21 cities in Guangdong Province from 2009 to 2021. Second, the natural breakpoint method and trend surface analysis were used to identify the spatiotemporal differences in and spatial trends of these tourism ecological efficiencies. Finally, the geographical detector model was utilized to analyze the elements affecting the spatial and temporal differences in the tourism ecological efficiencies. Overall, the tourism ecological efficiencies of 21 cities in Guangdong Province are at a high level, showing obvious spatiotemporal changes. Compared with 2009 and 2021, the overall tourism ecological efficiencies of 21 cities in Guangdong Province shifted from a trend of high in the north, low in the south, low in the west, and high in the east to a trend of low in the north, low in the south, high in the west, and low in the east. The distribution in the north–south and east–west directions is in a “U” shape, and the spatial differences in the north–south and east–west directions are relatively significant. We suggest considering the roles of factors such as the development of the digital economy, the level of government intervention, the level of technical innovation, the driving force of transportation, the standard of the transportation infrastructure, and the standard of social consumption. This study provides a constructive approach to elevating the tourism ecological efficiencies of 21 cities in Guangdong Province with regards to the nine driving factors.