The family Noctuidae is one of the world’s most diverse, ecologically successful, and economically important animal lineages; with over 12,000 species in ~1150 genera. We inferred a phylogeny based on eight protein-coding genes (>6,400 base pairs) for the global fauna, greatly expanding upon previous attempts to stabilize the higher classification of Noctuidae by sampling 70 of the 76 widely recognized family-group taxa: 20 of the 21 subfamilies, 32 of the 35 tribes, and 18 of the 20 subtribes. For nearly half of the 341 genera included we sampled their type species. We evaluated seventeen subfamily-level taxa in detail; discussing adult and larval morphology, life history data, and taxonomic implications of our results. We significantly alter current concepts of Acontiinae, Condicinae, Eustrotiinae, Metoponiinae, and Stiriinae. We lowered Bryophilinae and Eriopinae to Bryophilini stat. rev. and Eriopini stat. rev. within Noctuinae. Our results also supported recognition of Cropiinae Keegan and Wagner subf. nov. Other nomenclatural changes we made are as follows. We moved “Acontia” viridifera (Hampson, 1910); “Azenia” virida Barnes and McDunnough, 1916; Aleptinoides; Austrazenia; Chalcoecia; Megalodes; and Trogotorna to Chamaecleini in Acontiinae. We moved Apaustis to Acontiinae and reinstated Emmelia as a valid genus in Acontiinae. We moved Allophyes and Meganephria to Cuculliinae. We moved “Plagiomimicus” navia (Harvey, 1875); Airamia; Alvaradoia; Hypoperigea; Neotarache; and Mesotrosta to Condicinae. We moved Axenus, Azenia, Metaponpneumata, Sexserrata, and Tristyla to Metoponiinae. We moved Pachythrix and “Paramiana” canoa (Barnes, 1907) to Noctuinae. Finally, we moved Cobubatha, Copibryophila, Homolagoa, Tripudia, and Tyta to Noctuidae incertae sedis.