The estimation of non-point source pollution loads into the Danjiangkou Reservoir is highly significant to environmental protection in the watershed. In order to overcome the drawbacks of traditional watershed numerical models, a base flow separation method was established coupled with a digital filtering method and a flux method. The digital filtering method has been used to separate the base flows of the Hanjiang, Tianhe, Duhe, Danjiang, Laoguan, and Qihe rivers. Based on daily discharge, base flow, and pollutant concentration data, the flux method was used to calculate the point source pollution load and non-point source pollution load. The results show that: (1) In the year 2013, the total inflow of the six rivers mentioned above accounted for 95.9% of the total inflow to the Danjiangkou Reservoir. The total pollution loads of chemical oxygen demand (CODMn) and total phosphorous (TP) from the six rivers were 58.20 × 103 t and 1.863 × 103 t, respectively, and the non-point source pollution loads were 39.82 × 103 t and 1.544 × 103 t, respectively, indicating that the non-point source pollution is a major factor (with a contribution rate of 68.4% for CODMn and 82.9% for TP). (2) The Hanjiang River is the most significant contributor of pollution loads to the Danjiangkou Reservoir, and its CODMn and TP contribution rates reached 79.3% and 83.2%, respectively. The Duhe River took the second place. (3) Non-point source pollution mainly occurred in the wet season in 2013, accounting for 80.8% and 90.9% of the total pollution loads of CODMn and TP, respectively. It is concluded that the emphasis of pollution control should be placed on non-point source pollution.