This paper investigates the impact of the dynamic hydraulic conditions on the kinetics of chlorine decay in water supply systems. A simulation framework has been developed for the scale-adaptive hydraulic and chlorine decay modelling under steady- and unsteady-state flows. An unsteady decay coefficient is defined which depends upon the absolute value of shear stress and the rate of change of shear stress for quasi-unsteady and unsteady-state flows. By coupling novel instrumentation technologies for continuous hydraulic monitoring and water quality sensors for in-pipe water quality sensing a pioneering experimental and analytical investigation was carried out in a water transmission main. The results were used to model monochloramine decay and these demonstrate that the dynamic hydraulic conditions have a significant impact on water quality deterioration. The spatial and temporal resolution of experimental data provides new insights for the near real-time modelling and management of water quality as well as highlighting the uncertainty and challenges of accurately modelling the loss of disinfectant in water supply networks.