Identifying the causes (climate vs. human activities) for hydrological variability is a major challenge in hydrology. This paper examines the flow regime shifts, changes in the climatic variables such as precipitation, evaporation, temperature, and crop area in the semi-arid Hailiutu catchment in the middle section of the Yellow River by performing several statistical analyses. The Pettitt test, cumulative sum charts (CUSUM), regime shift index (RSI) method, and harmonic analysis were carried out on annual, monthly, and daily discharges. Four major shifts in the flow regime have been detected in 1968, 1986, 1992 and 2001. Characteristics of the flow regime were analyzed in the five periods: 1957–1967, 1968–1985, 1986–1991, 1992–2000, and 2001–2007. From 1957 to 1967, the flow regime reflects quasi natural conditions of the high variability and larger amplitude of 6 months periodic fluctuations. The river peak flow was reduced by the construction of two reservoirs in the period 1968–1985. In the period of 1986–1991, the river discharge further decreased due to the combined influence of river diversions and increase of groundwater extractions for irrigation. In the fourth period of 1992–2000, the river discharge reached lowest flow and variation in corresponding to a large increase in crop area. The flow regime recovered, but not yet to natural status in the fifth period of 2001–2007. Climatic factors are found not likely responsible for the changes in the flow regime, but the changes in the flow regime are corresponding well to historical land use policy changes.