Water quality management is complicated with a variety of uncertainties and nonlinearities. This leads to difficulties in formulating and solving the resulting inexact nonlinear optimization problems. In this study, an inexact chance-constrained quadratic programming (ICCQP) model was developed for stream water quality management. A multi-segment stream water quality (MSWQ) simulation model was provided for establishing the relationship between environmental responses and pollution-control actions. The relationship was described by transformation matrices and vectors that could be used directly in a multi-point-source waste reduction (MWR) optimization model as water-quality constraints. The interval quadratic polynomials were employed to reflect the nonlinearities and uncertainties associated with wastewater treatment costs. Uncertainties associated with the water-quality parameters were projected into the transformation matrices and vectors through Monte Carlo simulation. Uncertainties derived from water quality standards were characterized as random variables with normal probability distributions. The proposed ICCQP model was applied to a water quality management problem in the Changsha section of the Xiangjiang River in China. The results demonstrated that the proposed optimization model could effectively communicate uncertainties into the optimization process, and generate inexact solutions containing a spectrum of wastewater treatment options. Decision alternatives could then be obtained by adjusting different combinations of the decision variables within their solution intervals. Solutions from the ICCQP model could be used to analyze tradeoffs between the wastewater treatment cost and system-failure risk due to inherent uncertainties. The results are valuable for supporting decision makers in seeking cost-effective water management strategies.