Research on the carbon and water use efficiency (CUE, WUE) in the Qinghai-Tibet Plateau (QTP) holds significant importance due to its implications in understanding and addressing global environmental challenges, particularly climate change. This study comprehensively explored the spatiotemporal distribution patterns and trends of WUE and CUE on the plateau from 2001 to 2018 using linear regression analysis and geostatistical methods. The results revealed a gradual decrease in WUE from southeast to northwest, showing a non-linear variation trend during the study period. CUE exhibited relatively minor spatial variations but demonstrated a significant decrease trend in the eastern regions. The results from the Random Forest algorithm and path analysis indicated that ecosystem respiration (Re) was the predominant controlling factor for WUE and CUE in the cold alpine (PA) region. In the temperate, warm temperate (Te&WT) region, temperature emerged as the primary determinant for WUE, while Leaf Area Index (LAI) served as the absolute dominant factor for CUE. Additionally, LAI also played a crucial role in determining WUE and CUE in the tropical and subtropical (Tr&S) region. Partial correlation analysis highlighted the heterogeneity in the responses of WUE and CUE to environmental changes across different regional climates and vegetation types. The findings emphasized the significant impact of biological factors on terrestrial carbon and water cycling processes (WUE and CUE) within the context of global climate change. Furthermore, the study identified a potential linkage between WUE and CUE, with their relationship to vegetation dynamics showing significant variations across various ecosystems. WUE and CUE showed a positive correlation in the western regions, particularly in high-altitude areas, while a negative correlation was observed in eastern regions with high SOC. In the Te&WT and the Tr&S region, the increase of NDVI (Normalized difference vegetation index) suppressed the rise of both WUE and CUE, establishing a negative correlation between them. Conversely, in the PA region, a significant positive correlation trend between WUE and CUE was observed, indicating a positive response to the decrease in NDVI. These findings are of significant importance for advancing the understanding of and effectively addressing climate change, maintaining ecosystem stability, and promoting sustainable socio-economic development.