Acanthaceae is a family of tropical flowering plants with approximately 4000 species. Despite remarkable variation in morphological traits, research on patterns of character evolution has been limited by uncertain relationships among some of the major lineages. We sampled from these major lineages to estimate a phylogenomic framework using a combination of newly sequenced shotgun genome skims plus new and publicly available transcriptomes. We used OrthoFinder2 to infer a species tree with strong branch support. Except for the placement of Crabbea, our results corroborate the most recent chloroplast and nrITS sequence-based topology. Of 587 single copy loci, 10 were recovered for all 16 species; a RAxML tree estimated from these 10 loci resulted in the same topology as other datasets assembled in this study, with the exception of relationships among three sampled species of Barleria; however, branch support was lower compared to the tree reconstructed using more data. ABBA-BABA tests were conducted to investigate patterns of introgression involving Crabbea; few nucleotides supported alternative topologies. SplitsTree networks of the 587 loci and 6,136 trees revealed conflict among the branches leading to Andrographideae, Whitfieldieae, and Neuracanthus. A principal components analysis in treespace found no distinct clusters of trees. Our results strongly corroborate the previously published chloroplast and nr-ITS-based phylogeny of Acanthaceae with increased resolution among Barlerieae, Andrographideae, Whitfieldieae, and Neuracanthus. We propose that the tree presented here is the best estimate to date of Acanthaceae phylogeny. This advance in our knowledge of relationships will allow us to investigate character evolution and other phenomena within this diverse group of plants.