<p>Water use efficiency (WUE), as a pivotal indicator of the coupling degree within the carbon–water cycle of ecosystems, holds considerable importance in assessment of the carbon–water balance within terrestrial ecosystems. However, in the context of global warming, WUE evolution and its primary drivers on the Tibetan Plateau remain unclear. This study employed the ensemble empirical mode decomposition method and the random forest algorithm to decipher the nonlinear trends and drivers of WUE on the Tibetan Plateau in 2001–2020. Results indicated an annual mean WUE of 0.8088 gC/mm·m² across the plateau, with a spatial gradient reflecting decrease from the southeast toward the northwest. Areas manifesting monotonous trends of increase or decrease in WUE accounted for 23.64% and 9.69% of the total, respectively. Remarkably, 66.67% of the region exhibited trend reversals, i.e., 39.94% of the area of the Tibetan Plateau showed transition from a trend of increase to a trend of decrease, and 26.73% of the area demonstrated a shift from a trend of decrease to a trend of increase. Environmental factors accounted for 70.79% of the variability in WUE. The leaf area index and temperature served as the major driving forces of WUE variation.</p>