In order to investigate the situation of non-point source pollution in the Hongfeng Lake Basin, as well as the effects of prevention and control measures, the water quantity and water quality data of a typical sub-basin were used to calibrate and validate the water quantity and water quality parameters of the SWAT model. The validated SWAT model was used to simulate the spatiotemporal distribution of ammonia nitrogen, total nitrogen, and total phosphorus from 2001 to 2015 and investigate the effects of different measures on the control of non-point source pollution. The results show that the SWAT model has good applicability in the Hongfeng Lake Basin. The ammonia nitrogen, total nitrogen, and total phosphorus loads are mainly concentrated from April to September, accounting for 88.49%, 83.74%, and 97.36%, respectively, of the annual loads. The southwest and northeast sub-basins with large losses of nitrogen and phosphorus are key source areas of non-point source pollution. Measures such as fertilizer reduction and conversion of farmlands to forests and grasslands can effectively reduce the non-point source pollution, in particular, the total phosphorus pollution. The implementation of comprehensive management measures has a better effect in reducing nitrogen and phosphorus pollution.