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Abstract Neurolaeneae (Asteraceae) have a complicated taxonomic history. The tribe was described in 1927, but subsequently disregarded in 1977, and later reinstated as a tribe following a large‐scale phylogenetic analysis of Asteraceae in 2002. To date, this tribe has remained poorly studied and it has never been the subject of a comprehensive phylogenetic study. This work represents an integrative systematic approach to understanding evolutionary relationships in Neurolaeneae through a combination of comparative molecular phylogenetics and a detailed morphological database including a representative sample of 70% of genera and 33% of species in the tribe, respectively. Results from the phylogenetic analysis reveal that the Staurochlamys (previously recognized in the Coreopsideae) belongs to this tribe and indicates that recently proposed Calea alliance genera ( Calea , Laceanthos , Lemmatium , Meyeria , Podocalea , Tonalanthus ) and Tepuipappus should be recognized in a single, monophyletic Calea . We propose a novel circumscription of Neurolaeneae comprising 4 subtribes (Heptanthinae, recircumscribed Enydrinae and Neurolaeninae, and a new subtribe, Caleinae); 6 genera ( Calea , Enydra , Greenmaniella , Heptanthus , Neurolaena , Staurochlamys ) – 5 genera synonymized here; 10 subgenera (4 resurrected, 6 new); 20 sections (14 new); 12 series (7 new); 196 species (9 species synonymized here), 2 nothospecies, 2 subspecies and 4 varieties. We provide a morphological description and geographic distribution data for all subtribes, genera and infrageneric taxa. Also included is the first comprehensive list of all species of Neurolaeneae. This is a robust step toward understanding the diversity of this tribe, a group hitherto poorly known.