Large-scale ecological restoration, climate variability, and human water management are jointly reshaping river flow regimes, yet their combined effects on low and high flows remain poorly understood. We examined flow-regime changes in 13 typical basins of China's Loess Plateau, where extensive ecological restoration has occurred across a strong hydroclimatic gradient. Annual 7-day minimum and 1-day maximum flows during 1990–2020 were analyzed, and their joint trends were related to vegetation cover (VC), climatic water availability, and human water use (WU). Both low and high flows generally declined during 1990–2005 but increased during 2005–2020, indicating a shift from drying to wetting, with more pronounced changes in northern basins. Panel regression models showed that low-flow changes were most strongly associated with VC, whose estimated contribution shifted from negative to positive between the two periods, mainly in northern basins. In contrast, high-flow changes were consistently positively associated with short-term water availability, represented by maximum 14-day P−ET (precipitation minus evapotranspiration). During 2005–2020, WU and VC showed negative modeled contributions to high flows, suggesting partial attenuation of high-flow responses. Thus, the post-2005 wetting phase was characterized by a reversal of the modeled VC–low-flow association, while high-flow changes remained primarily associated with short-term water availability. Adaptive revegetation and high-flow risk management are both needed to sustain water security under a more variable hydroclimate.