To address the short lifetime of plasma‐activated water (PAW), this work reports on the application of ultralong‐lasting PAW for plant disease treatment. Compared with lettuce without ultralong‐lasting PAW treatment, the treated lettuce solution showed c. 1 log10 colony forming units mL−1 decrease in pathogens, as well as improvements in leaf area, leaf weight, root length, and root weight by 75%, 20%, 108.33%, and 150%, respectively. The leaf withering/root mortality rate of PAW‐treated plants was significantly lower than those of non‐PAW‐treated plants. Besides, disease defense‐related enzymes, such as catalase and β−1,3‐glucanase, were respectively enhanced by 112.5% and 5.13% in PAW‐treated lettuce, while the plant defense‐related genes were upregulated to respond to the pathogen's invasion.