The Indus Fan, located in the Arabian Sea, contains the bulk of the sediment eroded from the Western Himalaya and Karakoram. Scientific drilling in the Laxmi Basin by the International Ocean Discovery Program (IODP) provides an erosional record from the Indus River drainage dating back to 10.8 Ma, and with a single sample from 15.5 Ma. We dated detrital zircon grains by U-Pb geochronology to reconstruct how erosion patterns changed through time. Long-term increases in detrital zircon U-Pb components of 750–1200 Ma and 1500–2300 Ma show increasing preferential erosion of the Himalaya relative to the Karakoram at 7.99–7.78 Ma and more consistently starting by 5.87 Ma. An increase in the contribution of 1500–2300 Ma zircons starting by 1.56 Ma indicates significant unroofing of the Inner Lesser Himalaya (ILH) by that time. The trend in zircon U-Pb age populations is consistent with bulk sediment Nd isotope data implies greater zircon fertility in Himalayan bedrock compared to the Karakoram and Transhimalaya. The initial change in spatial erosion patterns at 7.0–5.87 Ma occurred during a time of drying climate in the Indus foreland. The increase in ILH erosion postdates the onset of dry-wet glacial-interglacial cycles suggesting some role for climate control. However, erosion driven by rising topography in response to formation of the Lesser Himalayan thrust duplex, especially during the Pliocene may also be important. The influence of the Nanga Parbat Massif to the bulk sediment flux is modest, in contrast to the situation in the eastern Himalaya syntaxis.