The distribution of genetic variation within species is the result of both historical and ongoing demographic and evolutionary processes. Here we examine how genetic variation in Euphorbia lomelii (Euphorbaceae) among populations in Baja Mexico to understand how region-wide historical processes may have influenced this species. Specifically, we examined how the formation of the Sea of Cortéz, separating mainland and peninsular populations, and range expansion caused by Post Pleistocene climate change have influenced genetic variation. Samples were obtained from 37 sites in Baja California and mainland Sonora with a total of 324 individuals genotyped using six nuclear DNA markers. Analysis of genetic structure showed that while there was considerable differentiation among sites (ΦST=0.19) there was no significant difference between mainland and peninsular populations. The genetic structure of E. lomelii also has a gradual change with a northward reduction in heterozygosity, most likely caused by the relatively rapid range expansion during the current interglacial period. This research is important in understanding how genetic structure is influenced by historical processes that have operated on species in this region.