The correlation between runoff and sediment challenges ecological preservation and sustainable development in the Yellow River Basin. An understanding of the key factors influencing variations in runoff and sediment transport in crucial river basins is essential for effective soil erosion management within the context of ecological and economic development. The Mann–Kendall test, Pettitt test, and Morlet wavelet analysis were employed in the Wuding River Basin to analyze the trends in runoff and sediment changes from 1960 to 2020. We explored the double cumulative curve method to assess the contribution rates of precipitation and human activities to the variability of runoff and sediment transport. We explored the primary factors driving the changes in runoff and sediment transport through random forest regression analysis. (1) From 1960 to 2020, annual precipitation in the Wuding River Basin increased minimally, while annual runoff and sediment transport decreased strongly with abrupt changes. Abrupt changes in annual runoff and sediment transport occurred in 1971 and 1979, respectively. (2) The relationship between runoff and sediment transport changed in approximately 1972 and 2000. The distribution of monthly runoff became more uniform during Periods II (1973–2001) and III (2002–2020) compared to that during the baseline period (1960–1972, Period I), while sediment transport became increasingly concentrated in the flood season. (3) During Period II, the contribution rates of climate and human activities to runoff and sediment transport were 11.94% and −14.5%, respectively, compared to the baseline period. During Period III, the contribution rates of climate and human activities to runoff and sediment transport were −11.9% and −17.7%, respectively. Human activities substantially reduced runoff and sediment, with greater impacts on sediment reduction. Climate weakly influenced basin sediment transport variations. (4) The normalized difference vegetation index (NDVI) and grassland area extent had the greatest impact on runoff, while the NDVI and forest area extent affected sediment transport.