The importance of natural water towers to water resource demand of the ecological environment and human activities is self-evident. They are also vulnerable and extremely sensitive to the effects of anthropogenic activities and climate change. However, water bodies change in water towers have not received sufficient attention. Therefore, Changbai Mountain, a typical high-latitude water tower, which is the source of Second Songhua River, Tumen River, and Yalu River, was selected to analyze the change of water bodies and its response to interaction of driving factors over recent decades by the methods of Correlation analysis and Geodetector. Results showed that there was an obviously divergent trend in water bodies, with a significant increase in surface water area (SWA) and a significant decrease in terrestrial water storage (TWS) in the high-latitude water tower, which was firstly found. The strong increase in water use was the dominant factor causing the divergent trends of water bodies in Tumen River. Changes in water bodies in the other two basins were all the result of the combined effects of climate change and anthropogenic activities. It is worth mentioning that snowpack had a noticeable influence on the change of water storage in this water tower. Meanwhile, reduced water conservation capacity due to degradation of complex forest-wetland ecosystems and altered snowmelt processes in the context of climate warming may be two key underlying causes. In addition, we innovatively found that the enhanced interactivity of the driving factors was an inherent reason. The results of this study will be beneficial for ecosystem conservation and stability of downstream water supply in this high-latitude water tower.