Mountainous areas have obvious spatial differences in topography and climate, which could further cause heterogeneity of ecosystem service (ES) trade-offs. The characteristics of ES trade-offs had been extensively studied, however, the driving mechanism of which is still unclear in mountainous areas. Focusing on the Hengduan Mountain region (HDM) in southwest China, this study quantified the spatial aggregation effects of ESs and their trade-offs using a spatial autocorrelation analysis, and identified the dominant drives for each ES trade-off across various geomorphological and climatic zones. In terms of the spatial distribution, ESs and their trade-offs have a significant positive spatial correlation, which was mainly manifested as high-high (H-H) and low-low (L-L) value aggregations. The dominant factors for some trade-offs differed across geomorphological and climatic zones. Land use type was the main factor in flat areas for paired water yield (WY) with soil conservation (SC) and carbon storage (C). In plateau (PLA) and mid-subtropical (MS) climate zones, the main factors were land use type and soil types for paired WY and C, respectively. Temperature had a higher contribution for paired C and SC in flat and plateau areas. For the other trade-offs, the dominant factor was constant for different zones. The normalized difference vegetation index (NDVI) and soil type were the main factors for paired net primary productivity (NPP) with SC and C respectively. For trade-offs between habitat quality (HQ) and other ESs, and those among multiple ESs, land use type was the dominant drive, and the influence decreased with the increase of topographic relief. Therefore, attention should be paid to the ecological effects of land use change in future urban planning and development. The study will help guide zoning regional spatial planning and achieve mountain sustainable development.