The presence of viruses in water is a major risk for human and animal health due to their high resistance to disinfection. Pulsed corona discharge plasma (PCDP) efficiently inactivates bacteria by causing damage to biological macromolecules, but its effect on waterborne virus has not been reported. This study evaluated the inactivation efficacy of PCDP to viruses using spring viremia of carp virus (SVCV) as a model. The results showed that 4-log10 reduction of SVCV infectivity in cells was reached after 120 s treatment, and there was no significant difference in survival of fish infected with SVCV inactivated by PCDP for 240 s or more longer compared to the control fish without virus challenge, thus confirming the feasibility of PCDP to waterborne virus inactivation. Moreover, the high input energy density caused by voltage significantly improved the inactivation efficiency. The further research indicated that reactive species (RS) generated by pulsed corona discharge firstly reacted with phosphoprotein (P) and polymerase complex proteins (L) through penetration into the SVCV virions, and then caused the loss of viral infectivity by damage to genome and other structural proteins. This study has significant implications for waterborne virus removal and development of novel disinfection technologies.