Lakes store the largest amount of Earth’s surface freshwater and their water storage is sensitive to both climate and human activity. Yet, the underlying mechanism driving lake water storage variability is poorly understood at the global scale due to the lack of high-quality global databases on lake volume dynamics and natural and anthropogenic forcings. Here, we integrate a newly compiled global lake volume dataset from multi-source satellite observations and recent advancements in global climate and human water use data into a statistical modeling framework to examine the drivers of lake volume variability globally. Using statistical models that incorporate observed changes in lake water storage, simulated/observed climate variables (e.g., precipitation, potential evapotranspiration, runoff, near-surface soil moisture), and simulated human water withdrawal, we attribute the recent lake water storage changes to natural and anthropogenic causes. We also analyze the amount of population affected by lake water loss. These results will advance the understanding of surface water storage dynamics and provide the imperative implications for water resources management.