Euphorbia subg. Chamaesyce contains around 600 species and includes the largest New World radiation within the Old World-centered genus Euphorbia. It is one of the few plant lineages to include members with C3, C4 and CAM photosynthesis, showing multiple adaptations to warm and dry habitats. The subgenus includes North American-centered groups that were previously treated at various taxonomic ranks under the names of "Agaloma ", "Poinsettia ", and "Chamaesyce ". Here we provide a well-resolved phylogeny of Euphorbia subg. Chamaesyce using nuclear ribosomal ITS and chloroplast ndhF sequences, with substantially increased taxon sampling compared to previous studies. Based on the phylogeny, we discuss the Old World origin of the subgenus, the evolution of cyathial morphology and growth forms, and then provide a formal sectional classification, with descriptions and species lists for each section or subsection we recognize.