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Water resources are increasingly under stress in Central Asia because downstream countries are highly dependent on upstream countries. Water is essential for irrigation and is becoming scarcer due to climate change and human activities. Based on 20 hydrological stations, this study firstly analyzed the annual and seasonal spatial-temporal changes of the river discharges, precipitation, and temperature in the Syr Darya River Basin and then the possible relationships between these factors were detected. Finally, the potential reasons for the river discharge variations have been discussed. The results show that the river discharges in the upper stream of the basin had significantly risen from 1930 to 2006, mainly due to the increase in temperature (approximately 0.3 degrees C per decade), which accelerated the melting of glaciers, while it decreased in the middle and lower regions due to the rising irrigation. In the middle of the basin, the expansion of the construction land (128.83 km(2)/year) and agricultural land (66.68 km(2)/year) from 1992 to 2015 has significantly augmented the water consumption. The operations of reservoirs and irrigation canals significantly intercepted the river discharge from the upper streams, causing a sharp decline in the river discharges in the middle and lower reaches of the Syr Darya River in 1973. The outcomes obtained from this study allowed us to understand the changes in the river discharges and provided essential information for effective water resource management in the Syr Darya River Basin.