Purpose Sediment dynamics in most large river basins are influenced by a variety of different natural and anthropogenic pressures, and disentangling these cumulative effects remains a challenge. This study determined the contemporary and historical sources of fine-grained (< 63-μm) sediment in a large, regulated river basin and linked changes in sources to activities in the basin. The river has seen declines in chinook salmon, sockeye salmon, and the endangered Nechako white sturgeon populations, and sediment (both fine-grained and sands) transport and deposition have been identified as potential causes of these declines. Materials and methods Samples of suspended sediment and potential source materials were collected from numerous sites distributed throughout the upper Nechako River Basin in British Columbia, Canada. A floodplain sediment core was also collected in order to reconstruct sediment sources over the last~70 years. Discriminating fingerprint properties were used within the MixSIAR model to apportion sources among sub-basins and land-use types. Results were compared to records of precipitation and Nechako River discharge trends, and to changes in landscape development. Results and discussion Contributions from the erosion of channel banks dominated the suspended sediment load at most sites. Changes in sediment sources during the 2015 field season reflected snowmelt and patterns of water release from the Nechako Reservoir that affected the sediment-carrying capacity of tributaries and the Nechako River main stem. Spatial variations in 2015 also reflected the distribution of land use (e.g., forested or agricultural land) as well as topography (e.g., slope steepness). Over the last~70 years, variations in sediment sources and the characteristics of the sediment (e.g., organic matter content and particle size composition) were linked to the construction of the Kenney Dam (operational in 1954) and the impacts of deforestation by the forestry and agricultural industries. Superimposed on these have been wildfires and a major mountain pine beetle infestation leading to higher erosion rates in the affected areas. Conclusions The sediment source fingerprinting technique, in combination with historical information on the hydrometeorology and the land use and river management in the basin, has provided valuable information with which to understand sediment dynamics in the Nechako River Basin. Such an approach can help to disentangle how large river systems respond to a combination of natural and anthropogenic pressures.