Water quality aspect with regard to dissolved oxygen was studied for a 24 kilometer stretch of Malaprabha River in Karnataka State, India. Main objective of the research was to simulate the predicted dissolved oxygen depletion due to the waste load allocation in the river with the ambient observed values of dissolved oxygen, and to ascertain the application of mathematical modeling for predicting the dissolved oxygen in a mixing zone. The entire river stretch selected for the study was divided in to four stations and water samples were collected from each station, and analyzed for different parameters. Station S1 was purely the upstream of the sewage discharge point and hence reflected the water quality of the river without pollution. Station S2 and downstream stations were the part of mixing zone where the discharged sewage at S2 kept spreading. Dissolved oxygen levels at these four stations were calculated through mathematical modeling, considering all variables that affect dissolved oxygen variation. Further, this predicted dissolved oxygen found with the application of mathematical modeling was then simulated with the actual observed values of dissolved oxygen in these four stations. The results were highly encouraging, with the predicted values almost agreeing with the observed values. Thus the application of such mathematical modeling may be useful for a river stretch where water pollution due to the discharge of effluents is expected, and will help the engineers in arriving at a proper waste-load allocation for the river.