Due to the heterogeneous terrains and unique alpine climate environment, the three‐dimensional differentiation of climatic impacts on vegetation change and its possible mechanism in the Pan‐Tibetan Plateau (PTP) are complex and lack adequate research. Hence, we here quantify the three‐dimensional differentiation of the contribution of climatic factors to vegetation change using the analysis of variance (ANOVA) method. Results indicate that the overall PTP has been warmer and wetter but partially drier, with a remarkable fractional vegetation coverage (FVC) increase since 2000. Moreover, the total areas with FVC changes accounting for approximately 49.3% of PTP are significantly driven by climate factors. Precipitation and potential evaporation predominate the vegetation change at relatively high altitudes and latitudes, while temperature affects the vegetation change at relatively low latitudes and parts of low elevations. Meanwhile, relative humidity dominates the vegetation change at middle altitudes and latitudes. Furthermore, the hydrothermal conditions and climate change magnitudes modulate the three‐dimensional differentiation. On the one hand, the effects of heat conditions on FVC change overwhelm the moisture conditions in alpine areas or warm and wet regions, in sharp contrast with the dominant role of water conditions in most dry areas. On the other hand, the spatial heterogeneity in climate change magnitudes influences the contribution of climatic factors in most hydrothermal conditions. Additionally, interventions challenging to quantify, such as climatic and mountainous hazards, anthropogenic activities, and vegetation feedback, will lead to the differentiation’s uncertainties. Our research hopefully provides theoretical support for national ecosystem management and major construction projects across PTP.