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Water use efficiency (WUE), defined as the ratio of gross primary productivity to evapotranspiration, is an important indicator of the trade-off between water loss and carbon gain. We used a biophysical process-based model to examine the relative importance of climate-induced changes in meteorological factors and leaf area index (LAI) on the changes in WUE in East Asia. Validation showed that our simulation could capture the magnitudes and variations of WUE at 18 flux sites in Asia. Regional results indicated that the highest WUE occurred in boreal forests at high latitudes and the lowest WUE in desert areas of China. Changes in meteorological factors negatively affected WUE in the northwestern, northern, and eastern study regions. Changes in LAI had determinant impacts on changes in WUE in most areas except for those with sparse or low-density vegetation (e.g., western interior China, southeast island countries) where meteorological factors dominated. We conclude that, aside from the impact of meteorological factors on WUE, climate-induced changes in LAI may play a prominent role in regulating WUE changes.