The upper Yangtze River flows southward on the southeastern Tibet characterizing by uniquely low and continuous relief. The river makes a sharp turn at Shigu, heading northeast, and forms the first bend of the Yangtze River. Many previous studies assumed southward flow of the ancestral Yangtze River from Shigu to the South China Sea. However, field evidence of southward flow of the paleo-Yangtze is lacking. In this paper we report our identification, based on detrital zircon U-Pb age distributions, of a range of fluvial sands left by the paleo-Yangtze in Tongdian, Madeng and Nanjian basins. Cosmogenic10Be and 26Al burial dating provides burial ages for these fluvial sands from 1.7 to over 8.7 Ma. Rerouting of the Yangtze River therefore occurred within the last 1.7 Ma, postdating the major uplift of the central Tibet. We attribute the rerouting of the Yangtze River to response to activation of the Dali fault system, and in a larger scale, initiation of crustal deformation by clockwise rotation around eastern Himalayan syntaxis 2–4 Ma ago. Reorganization of the Yangtze drainage pattern most likely reflects regional uplift and displacement due to lower crust flowing beneath major faults in the southeastern Tibet and Yunnan.