The rapid socio-economic development of the metropolitan area has led to the continuous deterioration of the ecological environment. This leads to intense competition and conflict between different spatial use types. Spatial conflict research is essential to achieve ecological-economic coordination and high-quality development. However, existing studies lack comprehensive and direct ecological-economic spatial conflicts, especially those on the spatial-temporal evolution and potential drivers of spatial conflict. In this study, we identified the ecological-economic spatial conflicts in the Nanjing metropolitan area in 2010, 2015, and 2020. This study used the random forest to analyze the factors that influenced the change of spatial conflict. Results show that: (1) From 2010 to 2020, the ecological-economic spatial conflict in the Nanjing metropolitan area changed significantly. (2) Land use change has an important effect on spatial conflicts, which are easily triggered by uncontrolled urban expansion, but ecological land can mitigate spatial conflicts. (3) Relevant driving factors of spatial conflicts show multi-level features, so the development of conflict reconciliation countermeasures needs to be tailored to local conditions. This study provides a significant foundation for the high-quality development of the Nanjing metropolitan area and provides a reference for the planning and management of the territorial space.