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Climate change and human activities exert significant influence on the water–sediment relationship in arid and semi-arid regions. Therefore, comprehending the underlying mechanisms is crucial for the effective management of water and soil resources, as well as integrated watershed management. This research focuses on the Kuye River watershed (KYH_W) in the middle reaches of the Yellow River in China, along with its sub-watersheds Wangdaohengtazi (WDHT_SW) and Xinmiaosi (XM_SW). This paper utilizes the Mann–Kendall non-parametric test and the double cumulative curve method to examine the interannual trends of runoff, sediment transport, precipitation, temperature, and NDVI factors. Furthermore, the method of the slope change ratio of cumulative quantity (SCRCQ) is utilized to quantitatively evaluate the impacts and contribution rates of climate change and human activities on water–sediment changes within each watershed. The results are as follows: (1) From 1969 to 2019, the entire watershed experienced a significant decrease in both runoff and sediment transport, with 1997 marking the year of abrupt change. However, following 2012, the KYH_W and WDHT_SW exhibited a noticeable rebound in runoff. (2) Human activities predominantly contribute to the reduction in water and sediment in the watershed. (3) After the abrupt change, between 1998 and 2011, the contribution rates of climate change and human activities to the annual runoff reduction in the entire KYH_W reached 33% and 64%, respectively. Moreover, these rates for sediment transport reduction reached 26% and 74%, respectively. Subsequently, after 2012, the contribution rates of both factors to the increase in watershed runoff reached 29% and 71%, respectively. Factors other than the NDVI, within human activities, played a dominant role in augmenting the watershed's runoff. (4) Prior to 2011, changes in vegetation cover resulting from the Grain for Green Program, as measured by the NDVI, emerged as the primary factor responsible for reduced runoff in the watershed. Conversely, factors other than the NDVI assumed dominance in reducing sediment transport. The SCRCQ method offers a quantitative approach to assessing water–sediment changes. Based on this method, the study further underscores the substantial impacts of climate change and human activities on variations in runoff and sediment transport within the KYH_W in the middle reaches of the Yellow River. Notably, the water–sediment changes in the KYH_W exhibit distinct stage-wise and spatial discrepancies, which warrant increased attention in future research endeavors. [ABSTRACT FROM AUTHOR]