Reservoir sedimentation is a critical issue worldwide, resulting in reduced storage volumes and, thus, reservoir efficiency. Moreover, sedimentation can also increase the flood risk at related facilities. In some cases, drawdown flushing of the reservoir is an appropriate management tool. However, there are various options as to how and when to perform such flushing, which should be optimized in order to maximize its efficiency and effectiveness. This paper proposes an innovative concept, based on an artificial neural network (ANN), to predict the volume of sediment flushed from the reservoir given distinct input parameters. The results obtained from a real-world study area indicate that there is a close correlation between the inputs—including peak discharge and duration of flushing—and the output (i.e., the volume of sediment). The developed ANN can readily be applied at the real-world study site, as a decision-support system for hydropower operators.