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Waterborne pathogens are a leading cause of disease and death worldwide. Ultraviolet (UV) irradiation is an effective method of drinking water treatment through the destruction of cells at the molecular level. Throughput capacity per unit volume of the UV unit is a major driver of the treatment process. In this study, we developed a microscale-based reactor in combination with UV radiation to determine the inactivation efficacy of bacteriophage MS2 and Escherichia coli. Using the microscale-based reactor, we achieved inactivation of more than 7 log colony forming units per mL of E. coli by 8 s and removal of more than 7.5 log plaque forming units per mL of bacteriophage MS2 by 8 min residence times. These values meet and surpass the standards set by the U.S.-Environmental Protection Agency and the World Health Organization for drinking water treatment technologies. Results from mathematical modeling suggest that the best fit model is obtained when we assume that more than a single photon directly damages E. coli cells and allows a transitional damaged state or further inactivation by additional photons. The successful application of a point-of-use UV water disinfection device to inactivate pathogens creates new opportunities for household and commercial water treatment globally. [ABSTRACT FROM AUTHOR]