Endorheic lakes are highly sensitive to climate variability and upstream water regulation, especially in arid and semi-arid regions. This study investigates the long-term decline of the Tashk-Bakhtegan lake system in southern Iran by integrating hydroclimatic variables, satellite-derived water extent dynamics, land cover change, and trend analysis. Results show a clear shift toward warmer and more water limited conditions in the basin during the study period from 1990 to 2024, where precipitation declined by approximately 2.0 mm yr^−1, while air temperature and potential evapotranspiration increased by about 0.05 °C yr^−1 and 4.7 mm yr^−1, respectively. Over the same period, lake area decreased by 22.5 km² yr^−1, whereas area of human-made reservoirs slightly increased by 0.41 km² yr^−1. Land cover changes in the basin further showed surface water loss, bare land expansion, and cropland decline. Breakpoint analysis identified a major transition around 2005-2006, when increasing climatic water stress coincided with rapid lake decline and a growing contrast between natural lake area and managed reservoir surfaces. These findings demonstrate that endorheic basins are especially susceptible when warming, drying trends coincide with unregulated upstream water extraction, underscoring the need for sustainable strategies to sustain terminal lake ecosystems.