A new species Mentzelia monoensis Brokaw and Hufford, endemic to Mono County, California, is described. Mentzelia monoensis, a hexaploid, is most similar to two widespread species, M. montana (Davidson) Davidson (tetraploid) and M. albicaulis (Douglas ex Hook.) Douglas ex Torr. & A. Gray (octoploid). The three species can be distinguished based on differences in floral bracts, fruits, and seeds. Mentzelia monoensis is commonly found in volcanic soils derived from the eruptions of Mono Craters and may exhibit edaphic specializations that limit its distribution.