Acanthaceae is a family of tropical flowering plants with over 4000 species, including Barleria (ca. 300 spp.), Justicia (ca. 400 spp.), and Ruellia (ca. 300 spp.). A 2008 estimate of phylogeny across the family by McDade et al. used four chloroplast loci (trnL-F region, rps16 intron, trnT-Land trnS-G intergenic spacers) and the nuclear ribosomal internal transcribed spacer. Several branches in the resulting tree had low support, particularly relationships between Barlerieae, Andrographideae, Neuracanthus, and Whitfieldieae. To test these relationships we used genome-scale sequence data from 16 species: four publicly available transcriptomes, seven newly sequenced leaf and flower transcriptomes, and five newly sequenced genome skims, to estimate a primarily nuclear phylogeny of the family. We de novo assembled transcriptomes using Trinity and identified coding regions using TransDecoder. Genome skims were de novo assembled using SPAdes and coding regions were predicted in Augustus. Amino acid sequences were used in OrthoFinder2 to identify 1,257,148 orthologous loci. Using several combinations of the data (6,136 orthogroups with all 16 species present, allowing for multiple copies; 587 single-copy loci for at least 9 out of 16 species; 10 single-copy loci with all species present) and estimation methods (STAG, RAxML, neighbor-net networks, PCAs) we explored phylogenetic signal in the data. A single topology was consistently recovered with high ML bootstrap support. The genome + transcriptome phylogeny corroborates the chloroplast + nrITS estimate, with the exception of the placement of Crabbea. The increased resolution and support for evolutionary relationships in the family will now allow us to infer patterns of character evolution, especially trends in flower color, anther, and pollen morphology.