The efficacy of the existing arsenal of antibiotics is continuously compromised by their indiscriminative and often excessive use. The antibiotic arsenal can be expanded with agents that have different mechanisms of activity to conventional drugs, such as plant-derived natural antimicrobial small molecules, yet these often lack sufficient activity and selectivity to fulfill the antibiotics requirements and conventional thermochemical methods of their transient activation may not be compatible with biomedical applications. Here, non-equilibrium conditions of atmospheric-pressure plasma are used for rapid, single-step potentiation of activity of select terpenes without the use of chemicals or heating. Substantial potentiation of activity against Staphylococcus aureus cells in planktonic and biofilm states is observed in both inherently antibacterial terpenes, e.g. terpinen-4-ol, and compounds generally considered to have limited effect against S. aureus, e.g. γ-terpinene. The improved biological activity may arise, at least in part, from the changes in the physico–chemical properties of the terpenes induced by plasma-generated chemical species and physical effects, such as electric fields and UV irradiation. This activation approach is generic, and thus can potentially be applied to other molecules and their mixtures in an effort to expand the range of effective antimicrobial agents for deactivation of pathogenic organisms in hygiene, medical and food applications.