Lakes have played a critical role in providing water and ecosystem services for people and other organisms in China for millennia. However, accelerating climate change and economic boom have resulted in unprecedented changes in these valuable lakes. Using Landsat images covering the entity of the country, we explored the changes in China’s lakes and the associated driving forces over the last 30 years (i.e., mid-1980s to 2015). We discovered that China’s lakes have changed with divergent regional trends: in the sparsely populated Tibetan Plateau, lakes are abundant, and the lake area has increased dramatically from 38,596 km2 to 46,831 km2 (i.e., increased by 8235 km2, or 21.3%), whereas in the densely populated northern and eastern regions, lakes are relatively scarce, and the lake area has decreased from 36,659 km2 to 33,657 km2 (i.e., decreased by 3002 km2, or 8.2%). In particular, severe lake decreases occurred in the Mongolia-Xinjiang Plateau and the Eastern Plain (–2151 km2). Statistical analyses indicated that climate was the most important factor controlling lake changes in the Tibetan Plateau, the Yun-Gui Plateau and the Northeast Plain. However, the strength of climatic control on lake changes was low in the Eastern Plain and the Mongolia-Xinjiang Plateau, where human activities, e.g., impoldering, irrigation, and mining, have caused serious impacts on lakes. Further lake changes will exacerbate regional imbalances between lake resources and population distribution and thus may increase the risk of water resource crises in China.