The quality of the drinking water distributed through the networks has become the main concern of most operators. This work focuses on one of the most important variables of the drinking water distribution networks (WDN) that use disinfection, chlorine. This powerful disinfectant must be dosed carefully in order to reduce disinfection byproducts (DBPs). The literature demonstrates researchers’ interest in modelling chlorine decay and using several different approaches. Nevertheless, the full-scale application of these models is far from being a reality in the supervision of water distribution networks. This paper combines the use of validated chlorine prediction models with an intensive study of a large amount of data and its influence on the model’s parameters. These parameters are estimated and validated using data coming from the Supervisory Control and Data Acquisition (SCADA) software, a full-scale water distribution system, and using off-line analytics. The result is a powerful methodology for calibrating a chlorine decay model on-line which coherently evolves over time along with the significant variables that influence it.