Dryland rivers sustain human and ecological systems across half of the Earth's land surface, underscoring the need to understand streamflow-sediment dynamics under climatic variability and human regulation. The Weihe River (WR), a representative dryland river, has undergone pronounced hydrological and sedimentary changes in recent decades. Using long-term observations from 1956 to 2024, this study synthesized spatiotemporal variations in streamflow and sediment and evaluated the relative roles of natural and human influences. Both streamflow and sediment load exhibited significant long-term declines (p < 0.05), together with clear regime shifts and spatial redistribution. The contribution of extreme streamflow and sediment events to annual streamflow and sediment load decreased over time, reflecting a diminished role of hydrological extremes under increasing regulation. Sediment contribution from the largest tributary (Jinghe River) of the Weihe River increased from 47.0% to 74.3%, whereas that from the Linjiacun-controlled reach declined from 31.9% to 16.5%. Human activities dominated these changes, accounting for 71.8% of streamflow reduction and 82.6% of sediment load reduction. Socioeconomic factors, including population growth, water consumption, and gross domestic product (GDP), accounted for similar to 50% of the observed declines and exerted a comparable influence to engineering interventions, indicating that water-use pressure can rival infrastructure-based sediment regulation. At the sub-basin scale, dominant drivers showed strong spatiotemporal heterogeneity, with socioeconomic influences increasingly important in the middle and lower reaches since the late 1990s. These results highlight the need for integrated watershed management in dryland rivers that incorporates socioeconomic regulation alongside engineering measures to maintain long-term water-sediment sustainability.