The Pearl River is one of the largest rivers entering the South China Sea, yet its initiation time remains debated, a topic we address using Pb isotopes in detrital K‐feldspar. Based on these Pb data, Eocene and Early Oligocene sandstones from the northern South China Sea are interpreted to have been supplied with sediment by proximal rivers draining the Cathaysia Block. In contrast, the Late Oligocene and Miocene sandstones are mainly derived from the western Pearl tributaries (e.g., Hongshui River), suggesting that the Pearl River had formed by the Late Oligocene. Detrital zircon data from the Beibuwan Basin previously suggested that the western tributaries flowed into this basin before being captured by the paleo‐Pearl River. These lines of evidence suggest that progressive headward erosion of the eastern Pearl River and late Oligocene integration of this large fluvial system can be linked to contemporaneous sea‐floor spreading of the South China Sea. Plain Language Summary The Pearl River is one of the largest rivers flowing into the South China Sea. However, when this river achieved its present drainage character remains debated. Here we report a comprehensive investigation of sand/sandstone provenance of the Pearl River as well as the Pearl River Mouth Basin (PRMB) using Pb isotopes measured in detrital K‐feldspar. Our results suggest that Eocene and Early Oligocene sandstones were mainly fed by proximal rivers within the Cathaysia Block, while the Late Oligocene samples are enriched in K‐feldspar grains from the Hongshui River, suggesting that the Pearl River had achieved its present character by the Late Oligocene. Early Oligocene deposits in the Beibuwan Basin share an indistinguishable detrital zircon provenance signal to that of the western tributaries of the Pearl River, indicating that the western tributaries likely flowed into the Beibuwan Basin before being captured by the paleo‐Pearl River. Taken together, this evidence suggest that progressive headward erosion of the eastern Pearl River triggered by the subsidence of PRMB and sea‐floor spreading of the South China Sea played an important role in the late Oligocene integration of this large fluvial system. Key Points Sedimentary provenance of the Pearl River and Pearl River Mouth Basin constrained using detrital K‐feldspar Pb isotopes Pb isotopic data indicate that the Pearl River achieved its present character by the Late Oligocene The opening of the South China Sea played an important role in the drainage reorganization of the Pearl River