The emergence of the Tibetan Plateau is one of the most significant geological events in East Asia. The Central Qilian Shan connects North and South Qilian Shan in the northeastern part of the Tibetan Plateau. However, the exhumation history of the Central Qilian Block from the Mesozoic to Cenozoic remains unclear. Determining the cooling ages of detrital zircon and apatite in modern river sediments is an ideal method for tracing the evolutionary processes of orogenic belts. In this study, we present the first single-grain detrital apatite (153) and zircon fission-track (108) data for the Huangshui River sediments from the Central Qilian Shan. The decomposition of the dataset revealed major Mesozoic and Cenozoic age peaks at ca. 145–93, and 11 Ma. The Central Qilian Shan entered the intracontinental orogeny stage dating back to the Cretaceous (ca. 145–93 Ma) and Late Cenozoic (ca. 11 Ma) caused by the subduction of the Neo-Tethys and Indian–Asian collision. Therefore, we propose that the geomorphic framework of the northeastern margin of the Tibetan Plateau was initially established during the Mesozoic and further consolidated in the Late Miocene.