Podostemaceae are a clade of aquatic flowering plants that form important components of tropical river ecosystems. Species in the family exhibit highly derived growth forms and high vegetative phenotypic plasticity, both of which contribute to taxonomic confusion. The backbone phylogeny of the family remains poorly resolved, many species remain to be included in a molecular phylogenetic analysis, and the monophyly of many taxa remains to be tested. To address these issues, we assembled sequence data for 73 protein-coding plastid genes from 132 samples representing 68 species (∼23% of described species) that span the breadth of most major taxonomic, morphological, and biogeographic groups of Podostemaceae. With these data, we conducted the first plastid phylogenomic analysis of the family with broad taxon sampling. These analyses resolved most nodes with high support, including relationships not recovered in previous analyses. No evidence of widespread, well-supported conflict among individual plastid genes and the concatenated phylogeny was observed. We present new evidence that four genera (Apinagia, Marathrum, Oserya, and Podostemum), as well as four species, are not monophyletic. In particular, we show that Podostemum flagelliforme should not be included in Podostemum and is better recognized as Devillea flagelliformis, and that Marathrum capillaceum is embedded within Lophogyne s.l. and should be recognized as Lophogyne capillacea. We also place a previously unsampled and undescribed species that likely represents a new genus. In contrast to previous studies, the neotropical genera Diamantina, Ceratolacis, Cipoia, and Podostemum are resolved as successive sister groups to a clade of all paleotropical Podostemoideae taxa sampled, suggesting a single dispersal event from the neotropics to the paleotropics in the history of the subfamily. These results provide a strong basis for improving the classification of Podostemaceae and a framework for future phylogenomic studies of the clade employing data from the nuclear genome.