Lakes are indispensable to ecological balance, supporting biodiversity and human welfare. Despite their importance, lakes around the globe are diminishing at an alarming rate, presenting substantial environmental challenges exacerbated by climate variability and human-induced pressures, such as unsustainable land management and excessive water withdrawals. This study offers an extensive analysis of the desiccation phenomena affecting major lakes on the Iranian plateau, dissecting the complex interplay of contributing factors. We examine meteorological, hydrological, and agricultural drought conditions using indices like SPI, SDI, and SPEI to gain nuanced insights into drought dynamics. This study sheds light on the factors that contribute to the drying up of lakes and quantifies the impact of anthropogenic and climatic drivers on this phenomenon. The findings indicate that the area of all lakes has declined dramatically after the change point, ranging from 51% in the Urmia Lake to an impressive rate (i.e. 100%) in Southern Hamun. Despite the stable rate of meteorological droughts (increasing in temperature by about 1 °C since the 90s and stable precipitation patterns across most basins), the research highlights the ongoing struggle against severe hydrological and agricultural drought conditions. The study delineates the predominant role of anthropogenic activities in the diminishing lake inflows and the consequential drying of the lake, accounting for approximately 100 % in five of the seven lakes.