The employment of ultraviolet (UV) disinfection in secondary water supply (SWS) systems has been a prevalent practice in recent years in China. However, highly fluctuating flow rates make the regular running of such UV disinfection reactors (i.e., lighting all the lamps all the time) a considerable waste of energy. In this study, an economical-running strategy, which consisted of various lamp operation modes for different time periods, was developed for a 6-lamp UV disinfection reactor in a SWS system. Reactor performances with lamp modes of different lamp output powers (LOPs) were simulated with computational fluid dynamics. Results show that the flow rate in the SWS system varied significantly in a day but shared similar daily variation patterns in the long term. This provided the basis for the economical running of the reactor by reducing the LOP periodically. The optimal lamp mode for a constant LOP was determined by comparing the corresponding reduction equivalent fluences (REFs), which was always found with the on-off switching solution (i.e., switching on/off the lamps according to the flow rates). The mixing efficiency factors (MEFs) of the reactor with various lamp modes were also discussed. The developed economical-running strategy for the reactor could save 32% of energy. This study established a methodology for the economical-running strategy development for UV disinfection reactors in SWS systems and provided an insight into the reactor performance at reduced LOPs.