The Weihe River Basin above the Hua-xian hydrological station, a section of about 10.65×10⁴ km², was selected as the study area. Based on the identification of critical source areas of non-point source (NPS) pollution output, six schemes and 34 scenarios were set, and the effects of various management measures of NPS under different hydrological years (wet, normal, and dry) were simulated. NPS loads of nitrogen and phosphorus were closely related with rainfall, and the distribution of sediment load had good correlations with that of attached nitrogen and phosphorus NPS loads. The effect of soil and water conservation measures on the reduction of nitrogen and phosphorus was the most obvious among the single measures. The effect of reducing the proportion of surface layer soil fertilizer rate and total fertilization on the reduction of mineral phosphorus and total phosphorus was obvious. The effect of improving irrigation methods and reducing irrigation water use on the control of nitrogen and phosphorus losses was more obvious than fertilization. Comprehensive measures significantly contributed in the reduction of all NPS polluttants. With the control of comprehensive measures, the maximum load reduction rates of organic nitrogen, organic phosphorus, ammonia nitrogen, nitrite nitrogen, nitrate nitrogen, mineral phosphorus, total nitrogen, and total phosphorus were, respectively, 29.42%, 32.90%, 24.99%, 21.18%, 20.23%, 29.45%, 22.69%, and 30.67% in the normal year.