Aeolian activity on the Tibetan Plateau (TP) has profound effect on the Asian and global climate. In the southern TP, loess deposition widely occurred associated with the massive glaciers and large rivers, recording the interplay history among the aeolian activity, atmosphere, and cryosphere. However, the initiation age of the loess and the factor controlling the loess formation are still controversial. Here, three drilling cores were retrieved from Linzhi area, in the eastern Yarlung Zangbo River Basin of the southern TP, which reached the bedrock and documented the loess development in the southern TP. Based on the optically stimulated luminescence, electron spin resonance, paleomagnetism dating and relative paleointensity correlation, the basal age of the drilling core was constrained at 584 ka revealing the onset of significant aeolian activity on the southern TP. Synthesize this study and previous work on the loess age across the TP, three stages were identified, namely 3600, 2800–2700, and 1200–600 ka, with the age trending younger from north to south. Extensive loess development on the TP occurred between 1200 and 600 ka, which was mainly ascribed to the global cooling during the mid-Pleistocene Transition. During this time, the ampler glaciers extent significantly expanded, westerly displaced southward and the wind intensity also intensified on the TP, which resulted in the enhancement of dust generation, arid and windy condition, leading to the loess preservation and development on the TP. Moreover, numerous evidences suggested that the glaciers on the TP may significantly developed since 800 ka, then enlarged at 500–600 ka, which may lead to the massive dust/loess input to the TP, Chinese Loess Plateau and north Pacific Ocean.