Opuntia nicholii is not commonly encountered, occurring in isolated locations in far northern Arizona and southern Utah. The plants can be large and sprawling, stretching up to 8-feet across or more with each cladode 6- to 14-inches long. Major spines are 2- to 6-inches long and stout. Fruits are 1- to 2-inches long. Seeds are large. The Flora of North America reports that O. nicholii grows in “barren areas with saltbush and ephedra, limestone or red, sandy soils,” around 4000 ft. The plants can resemble O. polyacantha rhodantha or stout-spined O. polyacantha hystricina, but only superficially. Some plants of O. nicholii vary from typical spination; perhaps through introgression with O. aurea. See the original description. Opuntia nicholii is hexaploid.
Even though the plants are large, some botanists proposed that O. nicholii was a variety of the smaller O. polyacantha rather than a distinct species. However, O. nicholii is hexaploid, whereas O. polyacantha is tetraploid. Like O. polyacantha, the fruits of O. nicholii are dry at maturity and the seeds are large. Hybridization with O. aurea and O. phaeacantha occurs.