Production of ethanol by the yeast Saccharomyces cerevisiae is a process of global importance. In these processes, productivities and yields are pushed to their maximum possible values leading to cellular stress. Transient and lasting enhancements in tolerance and performance have been obtained by genetic engineering, forced evolution, and exposure to moderate levels of chemical and/or physical stimuli, yet the drawbacks of these methods include cost, and multi-step, complex and lengthy treatment protocols. Here, plasma agitation is shown to rapidly induce desirable phenotypic changes in S. cerevisiae after a single treatment, resulting in improved conversion of glucose to ethanol. With a complex environment rich in energetic electrons, highly-reactive chemical species, photons, and gas flow effects, plasma treatment simultaneously mimics exposure to multiple environmental stressors. A single treatment of up to 10 minutes performed using an atmospheric pressure plasma jet was sufficient to induce changes in cell membrane structure, and increased hexokinase 2 activity and secondary metabolite production. These results suggest that plasma treatment is a promising strategy that can contribute to improving metabolic activity in industrial microbial strains, and thus the practicality and economics of industrial fermentations.