Freezing temperatures strongly influence vegetation in the hottest desert of North America, in part determining both its overall boundary and distributions of plant species within. To evaluate recent variability of freezing temperatures in this context, minimum temperature data from weather stations in the Sonoran Desert are examined. Data show widespread warming trends in winter and spring, decreased frequency of freezing temperatures, lengthening of the freeze-free season, and increased minimum temperatures per winter year. Local land use and multidecadal modes of the global climate system such as the Pacific decadal oscillation and the Atlantic multidecadal oscillation do not appear to be principal drivers of this warming. Minimum temperature variability in the Sonoran Desert does, however, correspond to global temperature variability attributed to human-dominated global warming. With warming expected to continue at faster rates throughout the 21st century, potential ecological responses may include contraction of the overall boundary of the Sonoran Desert in the south-east and expansion northward, eastward, and upward in elevation, as well as changes to distributions of plant species within and other characteristics of Sonoran Desert ecosystems. Potential trajectories of vegetation change in the Sonoran Desert region may be affected or made more difficult to predict by uncertain changes in warm season precipitation variability and fire. Opportunities now exist to investigate ecosystem response to regional climate disturbance, as well as to anticipate and plan for continued warming in the Sonoran Desert region.