Quality of water is of utmost importance for its intended use for any purpose. The river or stream ecology completely depends on DO concentration levels, and any absence or below the critical value will adversely affect the ecology of the river, and hence the flora and fauna of the water body. A 24 km stretch of Malaprabha river, near Belgaum in Karnataka State of India was selected for the application of mathematical modeling to predict the DO variation, due to the impact of organic loading from the Khanapur town. The entire stretch was divided into 16 transects, and variation in DO was predicted through the application of mathematical modeling, and simulated with the observed values of DO at each transect. The results agreed with the observed DO concentrations at each transect with little variation. Average DO values recorded at Station Slis 7.44 mg/L, the lowest DO value recorded at Station S2 with the minimum value of 6.98 mg/L due to the sewage disposal from Kanapur town. The predicted DO values at station S1 and S2 are 7.4 mg/L and 6.95 mg/L respectively. The measured values are in agreement with predicted values from the modeling. This study was conducted during the pre-monsoon season of 2005 - 2006 in which the DO values generally would be minimum. The application of predicting the DO in mixing zone of river may be the best strategy for waste load allocation to guide the practicing engineers and administrators to limit the organic loading in rivers and streams. This will help the decision makers in implementing the pollution prevention schemes of the region and to maintain the health of the riverine system.