Changes in water and sediment conditions in the Upper Yellow River Basin (UYRB), which contains the ecological barrier and “water tower” of the entire Yellow River Basin, directly affect the development of the downstream ecological environment. In this study, the impacts of recent and potential land use and climate changes on runoff and sediment load were investigated through statistical analysis, land-use maps, scenario estimations, and hydrological modelling. The temporal trends and abrupt changes in hydro-meteorological elements from 1957-2010 were analysed using linear regressions and moving-t tests. Transformations in land use from 1990 to 2014 were determined using a transfer matrix analysis. The back propagation neural network was constructed to modify and integrate several general climate models, and it projected the climate change evolution characteristics in the UYRB from 2021 to 2100 under different emission scenarios. On this basis, the effects of recent and potential land use and climate changes on runoff and sediment load were quantified using the Soil and Water Assessment Tool (SWAT) hydrological model and fifteen climate scenarios, respectively. The results show a significant decreasing trends for both runoff and sediment loads with warmer and wetter climate conditions in the past 50 years. An abrupt change in runoff occurred in 1990, and a notable change in sediment load occurred in 2000 which was defined as the dividing year of the study period. The warm and wet climate characteristics of the UYRB will continue from 2021 to 2100. Over the past 20 years, the transformation of land use in the URYB has intensified. Therefore, land use changes between 1990 and 2000 show significant increasing wetland trends and decreasing bare land and grassland trends. The SWAT simulation results indicated that climate changes have had a more significant impact on runoff than land use changes in the past 20 years, increasing runoff by 6.32%. Both land use and climate changes have great impacts on sediment load reduction. For the next 80 years, the potential land use change demonstrated greater impacts on runoff and sediment load than climate changes. The runoff and sediment load exhibited different trends under various climate conditions and emission scenarios. The results obtained in this study can provide useful information for water resource management, soil and water conservation, and ecological protection in the UYRB.