The gypsophilic flora of the Chihuahuan Desert forms a large and potentially old edaphic assemblage. We examine the age and biogeography of gypsophily in Tiquilia subg. Eddya, a Chihuahuan Desert plant group entirely composed of gypsophiles (restricted to gypsum) and gypsovags (growing on and off gypsum). A strongly supported phylogeny of the subgenus was generated using sequence data from matK, ndhF, rps16, ITS, and waxy. Combined analyses of these data suggest that the most recent common ancestor of subg. Eddya was a gypsovag and that gypsophily has evolved twice. Individual DNA sequence region analyses that include a broad geographic sampling of all species in the subgenus reveal a complex evolutionary history shared among the narrowly distributed gypsophiles T. tuberculata and T. turneri and the gypsovags T. gossypina and T. mexicana, including putative hybridization. They also reveal a high level of geographically correlated intraspecific variation in the widespread gypsophile T. hispidissima. Gypsophily is inferred to have been present in subg. Eddya by the early Pliocene. The concordance of the biogeographic patterns of gypsophily in subg. Eddya with that of other Chihuahuan Desert gypsophiles suggests that a broad phylogeographic pattern may be shared among many gypsophilic plant groups in this region.