A modeling study of the Danshui River, Taiwan, reveals that in-stream BOD deoxygenation rates vary significantly along the river as a result of the highly variable strength of wastewater discharges, which directly reflect the effluent characteristics. A comprehensive field data gathering and lab analysis effort for the study site is presented. Results of the data analyses yielded spatially variable CBOD deoxygenation and nitrification rates, which were incorporated in a model of the river. The model results indicate significant improvement of model calibration, thus enhancing the predictive capability of the model for its use in water quality management. To maximize the benefits of pollution control for the Danshui River system and to achieve the water quality management goal, concurrent reductions of CBOD and ammonia loads, instead of phased reduction of CBOD followed by ammonia reduction, are strongly recommended by the model results.