With the most prominent topography on Earth, the Tibetan Plateau has profound influences on the hydrologic cycle and climate dynamics in Asia. However, the regional uplift history of the Tibetan Plateau remains highly debated. Here, we use europium anomalies and LREE/HREE ratio in detrital zircon, combined with whole-rock La/YbN ratio, to constrain the crustal thickness and topographic evolution of the Gangdese mountains in southern Tibet. Europium anomaly, controlled by pressure-sensitive minerals plagioclase and garnet, has been shown to correlate with crustal thickness. Our results reveal contrasting crustal thickening histories of the eastern (east of ∼88°E) and western (west of ∼88°E) parts of the Gangdese. Prior to the India-Eurasia collision (∼60–55 Ma), the crust of the eastern Gangdese thickened continuously from ∼40 km to nearly 60 km, while the western Gangdese maintained a mildly thickened crust of ∼50 km. Both parts underwent substantial thinning (to 40–45 km) immediately before the India-Eurasia collision, but the eastern Gangdese re-thickened rapidly afterwards. In the western Gangdese, post-collisional thickening was delayed until ∼40–20 Ma, which resulted in a mild elevation of ∼2000 m for most areas of southern Tibet until the late Oligocene. This diachronous uplift of the Gangdese after collision may have resulted from more mantle-derived magma additions in the eastern Gangdese before collision, which could rheologically weaken its lithosphere. We suggest that the diachronous uplift of the Gangdese after the India-Eurasia collision may have dominated the moisture transfer pattern across southern Tibet through the late Eocene and intensified the South Asian monsoon through the Oligocene-Miocene boundary (∼25–20 Ma).