The use of low‐temperature plasmas for bio‐decontamination and sterilization has been gaining increased attention. In this study, a two‐dimensional array of integrated coaxial microhollow micro‐discharges generated in dry air at atmospheric pressure is used to treat metal surfaces (gas‐phase) and solution (liquid‐phase) contaminated with a known concentration of feline calicivirus (FCV). FCV acts as a surrogate for human norovirus, which is responsible for causing outbreaks of acute gastroenteritis in humans. The decontamination efficacy as well as the primary chemical pathways leading to virus inactivation in both the treatments are studied and compared. It is found that the humidity of the bio‐sample for gas‐phase treatment in dry air is required to achieve >5 log10 reduction in FCV titer within 3 min. The gas‐phase FCV inactivation is found to be due to a combination of ozone (O3) and reactive nitrogen species (RNS), most likely NOx. The liquid‐phase FCV inactivation mechanism is pH‐dependent and is primarily due to RNS, most likely acidified nitrites. O3 has a negligible effect on FCV suspended in solution. Previous studies performed in a batch reactor have shown that the inactivation pathways through O3 and RNS are mutually exclusive due to ozone poisoning at high NxOy concentrations. The present study employs a flow‐through system which avoids accumulation of reactive species and allows for the coexistence of NOx and O3 for the gas residence times used in this study, giving rise to these specific inactivation pathways.