Global warming and altered precipitation patterns are predicted to intensify the water loss in semi-arid and arid regions, and such regions in Turkey will be particularly affected. Moreover, water abstraction, not least for irrigation purposes, is expected to increase markedly, posing major threats to the water balance of the lakes and thus their biodiversity. Among the closed basins in Turkey, the Burdur Closed Basin (BCB), located in the southwest of Turkey, is expected to be most affected. The BCB includes several types of aquatic ecosystems which support high biodiversity, including one Ramsar site, six Important Bird Areas, and a considerable richness of native and endemic fish species. Therefore, it is essential to analyze the potential environmental impacts of climate change and increased water abstraction on BCB lakes and their biotic communities. Here, we combined historical data on ecosystems as well as meteorological, remote sensing, and ground-truth data to analyze the changes in the temperature and precipitation of the BCB, water surface areas, and land use, as well as the potential effects on waterbird and fish communities. We calculated the water budget to elucidate water availability in the basin over the last few decades and predicted future conditions based on rainfall and temperature forecasts using climate models. The Standardized Precipitation-Evapotranspiration Index (SPEI) was used to relate the water surface area to precipitation and temperature change in the basin. Crop-farming irrigation in the BCB has increased notably since 2004, leading to intensive water abstraction from the lakes and their inflows, as well as from ground water, to meet the increased demand for irrigation. The water abstraction from the lakes, inflows to the lakes, and the groundwater in the basin has increased the water loss in the catchment substantially. Remotely sensed data on lake surface areas showed a major shrinkage of shallow lakes in the last 40 years. Moreover, the largest lake in the basin, Lake Burdur, lost nearly half of its surface area, which is worrisome since the shallower areas are the most suitable for supporting high biodiversity. Climate models (CNRM-ESM2-1GCM for temperature and GFDL-ESM4-GCM for precipitation) suggest that from 2070, the BCB will face long-term, moderate-to-severe dry periods. This, and the increased demand for water for irrigation, along with climate change, may accelerate the drying of these lakes in the near future with devastating effects on the lake ecosystems and their biodiversity.