Qinghai-Tibetan Plateau is the most sensitive region to global warming on Earth. Qinghai Lake, the largest lake on the plateau, has experienced evident area variation during the past several decades. To quantify the area changes of Qinghai Lake, a satellite-based survey based on Landsat images from the 1980s to 2010s has been performed. In addition, meteorological data from all the seven available stations on Qinghai-Tibetan Plateau has been analyzed. Area of Qinghai Lake shrank ~2% during 1987-2005, and then increased ~3% from 2005-2016. Meanwhile, the average annual temperature increased 0.319 °C/10 y in the past 50 years, where the value is 0.415 °C/10 y from 2005-2016. The structural equation modeling (SEM) shows that precipitation is the primary factor influencing the area of Qinghai Lake. Moreover, temperature might be tightly correlated with precipitation, snow line, and evaporation, thereby indirectly causes alternations of the lake area. This study elucidated the significant area variation of water body on the Qinghai-Tibetan Plateau under global warming since 1980s.