Premise Recent phylogeographic work suggests the existence of latitudinal gradients in genetic diversity in northern Mexican plants, but very few studies have examined plants of the Chihuahuan Desert. Tidestromia lanuginosa is a morphologically variable annual species whose distribution includes the Chihuahuan Desert Region. Here we undertook phylogeographic analyses of chloroplast loci in this species to test whether genetic diversity and differentiation of Mexican populations of T. lanuginosa change along a latitudinal gradient and whether diversity is higher in Coahuila, consistent with ideas of lower plant community turnover during the Pleistocene. Methods Haplotype network, maximum likelihood tree, and Bayesian phylogenetic haplotype were reconstructed, and genetic diversity was assessed among 26 populations. Barrier analysis was used to explore barriers to gene flow. Results Four major population groups were identified, corresponding with physiographic provinces in Mexico. Each population group displayed high levels of genetic structure, haplotype, and nucleotide diversity. Diversity was highest in southern populations across the species as a whole and among the Chihuahuan Desert populations. Conclusions Tidestromia lanuginosa provides an important example of high phylogeographic and genetic diversity in plants of northern Mexico. Barriers to gene flow among the major population groups have most likely been due to a combination of orographic, climatic, and edaphic variables. The high genetic diversity of T. lanuginosa in southern and central Coahuila is consistent with the hypothesis of full‐glacial refugia for arid‐adapted plants in this area, and highlights the importance of this region as a center of diversity for the Chihuahuan Desert flora.