The eutrophication of rivers and lakes is becoming increasingly common, primarily because of pollution from agricultural non-point sources. We investigated the effects of optimized water and fertilizer treatments on agricultural non-point source pollution in the Nansi Lake region. The water heat carbon nitrogen simulator model was used to analyze water and nitrogen transport in Nansi Lake wheat fields. Four water and fertilizer treatments were set up: conventional fertilization and irrigation (CK), reduced controlled-release fertilizer and conventional irrigation (F2W1), an equal amount of controlled-release fertilizer and reduced irrigation (F1W2), and reduced controlled-release fertilizer and reduced irrigation (F2W2). The results indicated that the replacement of conventional fertilizers with controlled-release fertilizers, combined with reduced irrigation, led to reduced nitrogen loss. Compared with those of the CK, the cumulative nitrogen leaching and ammonia volatilization of F2W1 were reduced by 8.90 and 41.67%, respectively; under F1W2, the same parameters were reduced by 12.50 and 15.99%, respectively. Compared with the other treatments, F2W2 significantly reduced nitrogen loss while producing a stable yield. Compared with those of the CK, ammonia volatilization and nitrogen loss due to leaching were reduced by 29.17 and 27.13%, respectively, water and nitrogen use efficiencies increased by 11.38 and 17.80%, respectively. F2W2 showed the best performance among the treatments, considering water and fertilizer management. Our findings highlight the effectiveness of optimizing water and fertilizer application in improving the water and nitrogen use efficiency of wheat, which is of great significance for mitigating nitrogen loss from farmland in the Nansi Lake region.