A comprehensive understanding of the multiple factors affecting ecosystem services (ESs) supply and demand balance is essential for effective ecosystem management and policymaking. However, the importance of individual factors for ES balance is still unclear. Using Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) models and Structural Equation Modeling, I mapped the supply-demand balance of four types of ESs (carbon sequestration, water yield, soil conservation, and recreation) in Taihu Lake Basin, China, and quantified the causal relationships between multiple factors and ES balance. The results revealed spatial heterogeneity and imbalance in ES supply and demand in the basin, with the greatest imbalances in built-up city center areas. ES balance was influenced by multiple factors, but particularly normalized difference vegetation index (NDVI), elevation, precipitation, and human disturbance. For appropriate watershed management in the future, it is recommended that the number of small-scale community parks in city centers be increased and that green space be expanded in the suburbs, implementing of multi-objective ES management systems and step-by-step implementation plans, and optimizing the configuration of natural ecosystems by creating buffer strips for built-up areas. By carefully managing ES supply-demand balance and associated influencing factors, ecosystem status and human well-being in Taihu Lake Basin, and in other similar basins, can be substantially improved.