Recent phylogenomic analyses of sequence data from chloroplast and nuclear genomes as well as morphological and cytological analyses resolved long standing phylogenetic uncertainty in the rock daisy tribe (Perityleae; Asteraceae) and support reclassification at the generic level to reflect evolutionary relationships. The previously recognized genera Eutetras and Pericome were upheld as clades and continue to be recognized in the new classification. The large genus Perityle as treated in previous taxonomies was found not to be monophyletic and is thus reclassified in four genera, using the available names Laphamia (in an expanded sense), Galinsogeopsis (in an expanded sense), Nesothamnus, and Perityle (in a newly restricted sense). The type species of Perityle belongs to an early diverging lineage of the rock daisy tribe, in a clade with varied chromosome numbers of x = 11, 12, 13, 16, 18, or 19. In addition to the type (Perityle californica), Perityle now includes six other minimum-rank taxa of Perityle, all three taxa of Amauria, and the Desventuradas Islands endemic Lycapsus tenuifolius. Nesothamnus is reinstated as a monotypic genus for the Guadalupe Island endemic shrub Nesothamnus incana. Laphamia and Galinsogeopsis together constitute a clade of woody and herbaceous perennials or annuals with a stabilized base chromosome number of x = 17 (n = 17, 34, 51, 68) that have diversified throughout the Basin and Range Province and the Sierra Madre Occidental of the southwest US and northern Mexico. Laphamia and Galinsogeopsis have overlapping geographic distributions but can be distinguished by a combination of fruit and flower traits. This new generic classification of Perityleae resolves long standing conflict about the circumscription of Perityle without expanding the genus to encompass the entire subtribe Peritylinae and recognizes two independent evolutionary radiations onto island-like rocky habitats in western North America as taxonomically distinct components of this fascinating tribe of composites. To allow for this revised taxonomy, 46 new combinations in Galinsogeopsis, Laphamia, and Perityle are provided, and one new name, Laphamia sanchezii, is adopted.