Wilt disease in plants, which is caused by the soil-borne bacterial pathogen Ralstonia solanacearum, is one of the most devastating plant diseases. We previously detected bacterial wilt disease-inhibiting activity in an extract from yeast cells. In the present study, we purified this activity and identified one of the substances responsible for the activity as the amino acid histidine. The exogenous application of L-histidine, but not D-histidine, inhibited wilt disease in tomato and Arabidopsis plants without exhibiting any antibacterial activity. L-Histidine induced the expression of genes related to ethylene (ET) biosynthesis and signaling as well as the production of ET in tomato and Arabidopsis plants. L-Histidine-induced resistance to R. solanacearum was partially abolished in ein3-1, an ET-insensitive Arabidopsis mutant line. Resistance to the fungal pathogen Botrytis cinerea, which is known to require ET biosynthesis or signaling, was also induced by exogenously applied L-histidine. These results suggest that L-histidine induces resistance to R. solanacearum and B. cinerea partially through the activation of ET signaling in plants.