Lakes are important surface water bodies, and ongoing climate change is a growing threat to the hydrological cycle and water resource availability of lakes in arid regions. Accurately estimating different drivers’ contributions to lake water volume can enhance our understanding of lake variations in arid regions. In this study, we combined the land surface model and hydrological model, as well as statistical methods, to analyze the spatiotemporal heterogeneity of lake area changes and the factors affecting these changes during the past decades in Bosten Lake, Ulungur Lake, Ebinur Lake, and Sayram Lake, which are located in a typical dry region in China. The study revealed that the average amounts of river inflow, TWVF, lake ice sublimation, lake surface precipitation, and river outflow in the four lakes were 17.41 × 108 m3 yr−1, 6.60 × 108 m3 yr−1, 0.41 × 108 m3 yr−1, 0.98 × 108 m3 yr−1, and 9.12 × 108 m3 yr−1, respectively. We found that river inflow is the dominant factor affecting changes in open lake areas, while lake surface precipitation is the main factor affecting changes in closed lake areas. Our findings suggest that the main factors dominating the variability of lake water volume differ in different phases and lake types.