As the link connecting the South China Continent and the northern South China Sea (SCS), the Pearl River is the focus of sedimentology and petroleum geology research. Its evolutionary process and controlling factors are of great significance in revealing the East Asian continental landscape reorganization during the Late Cenozoic. Based on published data, 'source-to-sink' provenance analyses allow systematic deliberation on the birth and evolutionary history of the Pearl River. Close to the Oligocene/Miocene boundary, an abrupt shift in the sedimentary composition indicates significant westward and northward expansion of the river's watershed area, followed by the establishment of a near-modern fluvial network. This sedimentary change generally concurred with a series of regional geological events, including the onset of the Yangtze throughflow, large-scale development of the loess plateau, and formation of the northwestern arid zone and Asian Monsoon system. These major changes in the geology-climate-ecoenvironment system are in close response to the process of the Cenozoic Xizang (Tibetan) Plateau uplift. Consequently, the East Asian continental landscape and most of mid-Cenozoic drainage systems underwent critical reversion into east-tilting, or east-flowing networks.