The Huangshui River Basin, a region highly sensitive to climate change, was selected as a case study to investigate the evolution of extreme runoff at a regional scale and its climatic driving mechanisms. Daily average flow data were collected from seven stations in the basin. Mann–Kendall trend analysis and mutation tests were applied to assess the interannual variation of extreme runoff and its associations with extreme precipitation and high temperatures. The results indicate that over the past 60 years, the extremely high flow index in the basin has significantly decreased, whereas the extremely low flow index has notably increased. The frequency index did not exhibit any significant trend; however, all indices demonstrated persistence. Mutations in the high-flow index occurred around 2000, whereas mutations in the low-flow and frequency indices occurred in 2010. Cyclic analysis revealed that all indices exhibited a short cycle of approximately 3 years, whereas the frequency index also showed a long cycle of 32.5 years. Runoff variations were significantly correlated with an overall increase in extreme precipitation intensity, a decrease in precipitation duration, and an intensification of extreme high temperatures in the basin. Extremely high flows showed a positive correlation with extreme precipitation and negative correlation with extreme high temperatures. By contrast, extremely low flows exhibited a primary positive correlation with extreme high temperatures and weaker correlation with extreme precipitation. These findings provide critical insights for water resource management and flood disaster mitigation in the Huangshui River Basin.