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The Indus Fan derives sediment from the western Himalaya and Karakoram. Sediment from International Ocean Discovery Program drill sites in the eastern part of the fan coupled with data from an industrial well near the river mouth allow the weathering history of the region since ca. 16 Ma to be reconstructed. Clay minerals, bulk sediment geochemistry, and magnetic susceptibility were used to constrain degrees of chemical alteration. Diffuse reflectance spectroscopy was used to measure the abundance of moisture-sensitive minerals hematite and goethite. Indus Fan sediment is more weathered than Bengal Fan material, probably reflecting slow transport, despite the drier climate, which slows chemical weathering rates. Some chemical weathering proxies, such as K/Si or kaolinite/(illite + chlorite), show no temporal evolution, but illite crystallinity and the chemical index of alteration do have statistically measurable decreases over long time periods. Using these proxies, we suggest that sediment alteration was moderate and then increased from 13 to 11 Ma, remained high until 9 Ma, and then reduced from that time until 6 Ma in the context of reduced physical erosion during a time of increasing aridity as tracked by hematite/goethite values. The poorly defined reducing trend in weathering intensity is not clearly linked to global cooling and at least partly reflects regional climate change. Since 6 Ma, weathering has been weak but variable since a final reduction in alteration state after 3.5 Ma that correlates with the onset of Northern Hemispheric glaciation. Reduced or stable chemical weathering at a time of falling sedimentation rates is not consistent with models for Cenozoic global climate change that invoke greater Himalayan weathering fluxes drawing down atmospheric CO2 but are in accord with the idea of greater surface reactivity to weathering. [ABSTRACT FROM AUTHOR]