Results from molecular phylogenetic analyses have indicated that the two southernmost species in Mentzelia section Bicuspidaria, M. hirsutissima sensu lato and M. involucrata, form a clade in which M. hirsutissima is paraphyletic with respect to M. involucrata. Here we elevate M. hirsutissima S.Watson var. nesiotes I.M.Johnst. to specific rank, recognizing it as M. nesiotes (I.M.Johnst.) Brokaw & J.J.Schenk, thus rendering all three taxa monophyletic. Mentzelia nesiotes is allopatric relative to M. involucrata and M. hirsutissima sensu stricto, with all known populations of M. nesiotes occurring in northern Baja California Sur and nearby Pacific islands. Multivariate analyses of morphological differences determined that M. nesiotes and M. hirsutissima are best distinguished by capsule length, calyx length, and leaf intersinus width. Estimation of climate niches with MaxEnt inferred that M. nesiotes and M. hirsutissima showed minimal overlap in climate tolerances, with M. nesiotes inhabiting the Vizcaíno fog desert west of the Peninsular Ranges and M. hirsutissima inhabiting areas further north with higher precipitation and temperature fluctuations primarily east of the Peninsular Ranges. We provide updated circumscriptions of all three species, reduce M. hirsutissima var. stenophylla and M. involucrata var. megalantha to synonymy with their respective species, and designate the lectotype of M. hirsutissima.