As streamflow and sediment of the coarse sand area in the middle reaches of the Yellow River have experienced considerable change under the background of climate change and intensified human activities in recent years, it is of great importance to conduct research on their driving factors to predict future streamflow and sediment discharge of the Yellow River. We used annual precipitation, annual streamflow volume, and annual sediment discharge data from 15 hydrological stations located in the coarse sand area of the middle reaches of the Yellow River from 1956 to 2010. The Mann-Kendall trend test, Pettitt change point test, generalized additive model for location, scale, and shape model (GAMLSS), and comparison of cumulative slope change rate were applied to analyze the variation characteristics of these hydrological variables and to determine the driving factors of annual streamflow volume and annual sediment discharge. The results of the analyses are as follows: (1) The Mann-Kendall trend tests showed that annual precipitation demonstrated a non-significant decreasing trend at the 5% significance level, whereas annual streamflow volume and sediment discharge exhibited significant decreasing trends in the study area; (2) The Pettitt change point tests showed that the abrupt change of time-points for annual streamflow volume and sediment discharge occurred around 1972, 1985, and 1996; (3) The GAMLSS results indicated that the mean values of annual precipitation did not change with time, but the variance of annual precipitation showed a decreasing trend in all study areas; (4) The comparison of cumulative slope change rate showed that the influences of human activities on annual streamflow volume and sediment discharge were greater in the Kuye River basin than that in the Wuding River basin. Analyzing the driving factors of changes in annual streamflow volume and sediment discharge provides theoretical support for the rational allocation of water resources in the coarse sand area of the middle reaches of the Yellow River.