The low degree of development and utilization as well as the contradiction between supply and demand of water resources in Huangshui River basin are the main restricting factors of the local agricultural development. The study on the simulation of irrigation water loss based on the VSMB model has very important significance to strengthening regional water management and improving water resource utilization efficiency. Five groundwater wells were set up to carry out the farmland irrigation water infiltration and the experimental study on groundwater dynamic effect. Two soil moisture monitoring sites were set up in two typical plots of Daxia and Guanting irrigation area at the same time and TDR300 was used to monitor four kinds of deep soil moisture (10 cm, 30 cm, 50 cm and 70 cm). On this basis, the VSMB model was used to study the irrigation water loss in the irrigation area of Yellow River valley of Qinghai Province, including soil moisture content, the actual evapotranspiration, infiltration, runoff, groundwater buried depth and so on. The results showed that the water consumption caused by soil evaporation and crop transpiration accounted for 46.4% and 24.1% of the total precipitation plus irrigation, respectively, and the leakage accounted for 30.3% and 60.6% of the total precipitation plus irrigation, respectively, from March 1, 2013 to April 30, and from August 1 to September 30. The actual evaporation of the GT-TR1 and GT-TR2 sites in the whole year of 2013 was 632.6 mm and 646.9 mm, respectively, and the leakage accounted for 2.6% and 1.2% of the total precipitation plus irrigation, respectively. RMSE of the simulation results of the groundwater depth in Daxia irrigation area during the two periods was 92.3 mm and 27.7 mm, respectively. And RMSE of the simulation results of the water content of soil profile in the two monitoring sites of Guanting irrigation area was 2.04% and 5.81%, respectively, indicating that the simulation results were reliable.