In recent years, global climate change and intensified human activities have led to significant changes in the conditions of flow and sediment production in the Weihe River basin. It is of great significance to study the characteristics of runoff and sediment variation in this region for soil and water conservation in the Loess Plateau and the sustainable development of the basin. In this paper, based on the measured runoff and sediment data of the representative hydrological stations of the main stream of the Weihe River, Huaxian Station and Xianyang Station, for a total of 62 years from 1960 to 2021, the intra-annual and inter-annual variations of the runoff and sediment transport in the lower reaches of the Weihe River are investigated by using the methods of set-pair analysis, Mann-Kendall nonparametric test, and Morlet wavelet analysis. The results show that the seasonality of runoff and sediment variation at Huaxian and Xianyang stations is obvious, the degree of runoff-sediment connectivity at Huaxian station is higher in winter, while that at Xianyang station is higher in autumn, and the degree of runoff-sediment connectivity of the two stations is the lowest in summer. From the inter-annual point of view, the runoff and sediment at Huaxian and Xianyang stations show a fluctuating downward trend. The runoff volume of both stations changed abruptly in 1971; the sediment transport volume of Huaxian station changed abruptly in 2002, and the sediment transport volume of Xianyang station did not have any abrupt change point.