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Ultraviolet light in the UVC range is a commonly used disinfectant to control viruses in clinical settings and water treatment. Here, we employed an experimental evolution approach to investigate the adaptation of human echovirus 11 to disinfection by UVC, and characterized the underlying phenotypic and genotypic changes. Repeated exposure to UVC lead to a reduction in the UVC inactivation rate of approximately 15%. Time-series next generation sequencing data revealed that this adaptation to UVC was accompanied by a decrease in the echovirus 11 mutation rate. The inactivation efficiency of UVC was additionally compromised by a shift from first-order to biphasic inactivation kinetics, a form of “viral persistence”. Importantly, populations with biphasic inactivation kinetics also exhibited resistance to ribavirin, a mutagenic drug. Overall, our results indicate that while the ability of echovirus 11 to adapt to UVC is limited, resistance may have relevant consequences to disinfection in both clinical and water treatment contexts.