Cryptantha, an herbaceous plant genus of the Boraginaceae, subtribe Amsinckiinae, has an American amphitropical disjunct distribution, found in western North America and western South America, but not in the intervening tropics. In a previous study, Cryptantha was found to be polyphyletic and was split into five genera, including a weakly supported, potentially non-monophyletic Cryptantha s. s. In this and subsequent studies of the Amsinckiinae, interrelationshipswithin Cryptantha were generally not strongly supported and sample size was generally low. Here we analyze a greatly increased sampling of Cryptantha taxa using high-throughput, genome skimming data, in which we obtained the complete ribosomal cistron, the nearly complete chloroplast genome, and twenty-three mitochondrial genes. Our analyses have allowed for inference of clades within this complex with strong support. The occurrence of a non-monophyletic Cryptantha is confirmed, with three major clades obtained, termed here the Johnstonella/Albidae clade, the Maritimae clade, and a large Cryptantha core clade, each strongly supported as monophyletic. From these phylogenomic analyses, we assess the classification, character evolution, and phylogeographic history that elucidates the current amphitropical distribution of the group. Revealing the timing, direction, and number of times of dispersal between North and South America gives insight as to the origin of the great biodiversity of these regions.