Abstract The infrageneric classification of the genus Clerodendrum (Lamiaceae) has been highly problematic due to different concepts and subdivisions being applied to the treatment of Asian, Australian, and African species. Earlier molecular phylogenetic studies based on Sanger sequencing and limited sampling have indicated that previous morphology-based infrageneric classifications are not congruent with the phylogeny due to morphological convergence in many lineages. Advances in high-throughput DNA sequencing provide more information allowing more robust phylogenetic reconstruction at larger scale. We present the first comprehensive phylogenetic study of Clerodendrum that includes representatives of all previously recognized infrageneric taxa and using targeted sequencing data obtained from the Angiosperms353 enrichment to resolve the phylogenetic relationships. In agreement with previous phylogenetic work, our phylogeny shows that Asian and Australian species form a sister clade to an African Clade. Clerodendrum is monophyletic with the exclusion of some tropical coastal species, including some Australian species, which fall within a clade containing Volkameria and New World genera. We recognize two subgenera: subgen. Clerodendrum for Asian and Australian species and the new subgen. Afroclerodendrum for African and Malagasy species. Our findings support an infrageneric classification of Clerodendrum with a total of 13 sections based on molecular phylogenetic evidence and morphology that clearly accommodate the Asian, remaining Australian, and African species. Of these, we propose three new sections: sect. Albiflora, sect. Fortunata and sect. Megaflora for clades presenting unique morphological characters. The sectional classification and taxonomic consequences are discussed.