Caespitose and cold‐tolerant plants of Parthenium ligulatum (Jones) Barneby (Asteraceae) from a native population in the Uinta Basin, Utah, were uprooted, potted, and transferred to a greenhouse in California. Approximately two years after transfer, the plants flowered and subsequently were crossed to diploid guayule (Parthenium argentatum Gray), the rubber‐bearing species, native to the state of Durango, Mexico. Only female guayule × male P. ligulatum crosses produced F1 hybrids. Only crosses involving guayule as female parent and F1 plants as male parents produced backcross (BC,) plants. Hybrid plants were variable with respect to their growth habit, inflorescence, and leaf shape. Both parents and F1 hybrids had 2n = 36 chromosomes. Unlike the parents, however, meiosis was irregular in the hybrids which showed a range of 0–5 and an average of 2.1 univalents at metaphase I. Hybrids averaged 0.87 laggards at anaphase I and 0.83 micronuclei at the tetrad stage. The crossability of guayule and P. ligulatum, the high degree of chromosome pairing of the F1 hybrids, and the production of BC1 plants indicate that the two species are related in spite of their distinct morphological and ecological differences. This study suggests that the cold‐tolerance trait of P. ligulatum may be transferred to guayule through interspecific hybridization followed by backcrossing. The development of cold‐tolerant guayule cultivars is expected to expand the areas of guayule production beyond that of the Chihuahuan desert and similar climates.