Abstract Plant defense against pathogens depends on the action of several endogenously produced hormones, including jasmonic acid (JA) and ethylene. In certain defense responses, JA and ethylene signaling pathways synergize to activate a specific set of defense genes. Here, we describe the role of the Arabidopsis (Arabidopsis thaliana) APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) domain transcription factor ORA59 in JA and ethylene signaling and in defense. JA- and ethylene-responsive expression of several defense genes, including PLANT DEFENSIN1.2 (PDF1.2), depended on ORA59. As a result, overexpression of ORA59 caused increased resistance against the fungus Botrytis cinerea, whereas ORA59-silenced plants were more susceptible. Several AP2/ERF domain transcription factors have been suggested to be positive regulators of PDF1.2 gene expression based on overexpression in stably transformed plants. Using two different transient overexpression approaches, we found that only ORA59 and ERF1 were able to activate PDF1.2 gene expression, in contrast to the related proteins AtERF1 and AtERF2. Our results demonstrate that ORA59 is an essential integrator of the JA and ethylene signal transduction pathways and thereby provide new insight into the nature of the molecular components involved in the cross talk between these two hormones.