The superoxide (O2−)‐generating NADPH oxidases are crucial for the defense of plants against attack from pathogens; however, it remains unknown whether they also mediate responses against chewing insect herbivores. The transcripts of the respiratory burst NADPH oxidase homolog Narboh D in Nicotiana attenuate are rapidly and transiently elicited by wounding, and are amplified when Manduca sexta oral secretions (OS) are added to the wounds. The fatty‐acid‐amino‐acid‐conjugates (FACs), demonstrably the major elicitors in M. sexta OS, are responsible for the increase in Narboh D transcripts. Silencing Narboh D significantly reduced reactive oxygen species (ROS) levels after OS elicitation, but neither OS‐elicited jasmonic acid (JA) or JA‐isoleucine (JA‐Ile) bursts, pivotal hormones that regulates plant resistance to herbivores, nor early transcripts of herbivore defense‐related genes (NaJAR4 and NaPAL1), were influenced. However, late OS‐elicited increases in trypsin proteinase inhibitors (TPIs), as well as the transcript levels of defense genes such as polyphenol oxidase, TPI and Thionin were significantly reduced. In addition, Narboh D‐silenced plants were more vulnerable to insect herbivores, especially the larvae of the generalist Spodoptera littoralis. We thus conclude that Narboh D‐based defenses play an important role in late herbivore‐elicited responses.