Abstract A multidisciplinary study was conducted on the section of the Siwalik Group sediments, approximately 5000 m thick, exposed along the Karnali River. Analysis of facies, clay mineralogy and neodymium isotope compositions revealed significant changes in the sedimentary record, allowing discussion of their tectonic or climatic origin. Two major changes within the sedimentary fill were detected: the change from a meandering to a braided river system at ca 9.5 Ma and the change from a deep sandy braided to a shallow sandy braided river system at ca 6.5 Ma. The 9.5-Ma change in fluvial style is contemporaneous with an abrupt increase of ɛNd(0) values following a ɛNd(0) minimum. This evolution indicates a change in source material and erosion of Lesser Himalayan rocks within the Karnali catchment basin between 13 and 10 Ma. The tectonic activity along the Ramgarh thrust caused this local exhumation. By changing the proximity and morphology of relief, the forward propagation of the basal detachment to the main boundary thrust was responsible for the high gradient and sediment load required for the development of the braided river system. The change from a deep sandy braided to a shallow sandy braided river system at approximately 6.5 Ma was contemporaneous with a change in clay mineralogy towards smectite-/kaolinite-dominant assemblages. As no source rock change and no burial effect are detected at that time, the change in clay mineralogy is interpreted as resulting from differences in environmental conditions. The facies analysis shows abruptly and frequently increasing discharges by 6.5 Ma, and could be linked to an increase in seasonality, induced by intensification of the monsoon climate. The major fluvial changes deciphered along the Karnali section have been recognized from central to western Nepal, although they are diachronous. The change in clay mineralogy towards smectite-/kaolinite-rich assemblages and the slight decrease of ɛNd(0) have also been detected in the Bengal Fan sedimentary record, showing the extent and importance of the two major events recorded along the Karnali section.