The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) is an agriculturally important insect pest and causes significant economic loss due to its resistance to insecticide and high dispersal ability (i.e. long‐distance flyer). We performed comparative genomics analysis based on the recently released chromosome‐scale genome of the FAW to investigate the genetic mechanisms of FAWs defense system and flight ability. The gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione‐S‐transferase, were expanded in FAW, enabling its ability to detect and detoxify many plant secondary compounds. The chromosomal locations of five detoxification‐related genes (i.e. ABC, CCE, GST, P450, and UGT) were analyzed, which revealed the density of these genes across the FAW genome. Several genes like Mio, Sik2, CRTC, and Lpin were positively selected in FAW, which were associated with energy metabolism, lipid metabolism, and/or muscle development, and thus possibly contributed to the high flight ability of FAW. We also analyzed the homologs to antimicrobial genes reported in the Drosophila genome, and identified 2 attacins, 6 cecropins, 3 gloverins, and 2 moricins in FAW. The findings of this study will broadly expand our knowledge on the biology of the devastating FAW, and contribute to the development of new pest management strategies for the control of major agricultural pests like FAW.