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The Kyzylkum Desert, as a transition area of different dust source in Central Asia, provides and reserves a large amount of dust transported by different atmospheric circulation systems, affecting Uzbekistan and downwind East Asia. However, there remains very few investigations about sediment sources and control factors of the desert. We hereby first present a provenance study on the Kyzylkum Desert, utilizing detrital zircon U‐Pb ages of samples composed of desert sand, alluvial sediments from Amu Darya River and piedmont of Southwest Tianshan Mountains. The results reveal that the Southwest Tianshan Mountains contribute the majority of the Kyzylkum desert sand, and the river system, dominated by Syr Darya, controls the sediment provenance of the desert. Moreover, little contribution from the Kyzylkum and Nurata segments indicates that wind erosion on the bedrocks is weak. However, the aeolian process is still crucial but deposit and storage of dust are determined by local topography. Plain Language Summary: The Arid Central Asia is commonly considered one of the most important dust sources in the world. The Kyzylkum Desert, located in the center of the multiple dust sources in Central Asia, provides and receives a large amount of dust, affecting Uzbekistan and downwind East Asia. However, research on sediment sources and control factors in the area is under debate. We investigate the potential provenance, spatial variability, and transport patterns of sand in the Kyzylkum Desert using detrital zircon U–Pb geochronology on 10 sediment samples. The results reveal that the Southwest Tianshan Mountains contribute the majority of the Kyzylkum desert sand, however, the proximal provenances also have a significant influence on the formation of the desert. The geomorphologic history shows that, the river system, dominated by Syr Darya, controls the sediment provenance of the Kyzylkum Desert. The wind displays little influence on the rework and recycle process of Kyzylkum Desert, indicated by inhomogeneous composition between northwest and southeast desert. The unmixing model results show evidence of sediments from the Kyzylkum Desert transported to the piedmont areas, but the transport and deposition of dust are primarily controlled by topography. Key Points: Detrital zircon U‐Pb dating indicates that the Southwest Tianshan Mountains are the primary sediment source of the Kyzylkum DesertThe river system controls the sediment provenance of the Kyzylkum DesertTopography determines reserve positions of the aeolian sand and dust from Central Asian deserts [ABSTRACT FROM AUTHOR]