Desert Iguana habitat most often consists of sandy arroyos or other open areas with loose soils, but sometimes the species occurs on nearby rocky hillsides (Norris 1953; Grismer 2002, 2004). In most of its range, Desert Iguanas are typically found in Creosote Bush desert with hummocks of loose sand and patches of firm ground with scattered rocks, whereas in southern Baja they occur in subtropical arid shrub habitats (Norris 1953, Stebbins 2003, Venegas-Barrera et al. 2008). These lizards seek shelter both from heat and predators in rodent burrows or rock crevices (Grismer 2002, Revell 2005), and they may climb into bushes (Stebbins 2003).

The Desert Iguana is generally active from April-September, with limited activity at other times of the year dependent on environmental temperature, with the exception of populations on Catalina Island that are active throughout the year (Grismer 2004, Revell 2005, Venegas-Barrera et al. 2008). No specific information on hibernation is available. Activity patterns also vary throughout the day; individuals tend to bask early in the morning and are more likely to enter burrows later in the day (Grismer 2004).

The mean home range size of Desert Iguanas varies greatly among individuals (201–4,244 m²), but also differs among sexes (M = 1,462 m², F = 1,558 m²; Krekorian 1976). Conversely, there does not seem to be much sexual dimorphism in body size, including snout-vent length, head length, or head width (Dibble et al. 2008). Mean snout-vent length across the range is 115.43 mm, with a maximum of 148 mm (M. Packer et al. unpublished data). Males in Palm Springs, CA, had a mean body mass of 70.0 g with a range from 48.4 to 92.0 g (Singleton and McGarland 2018).

The Desert Iguana reproduces annually across its range (Mayhew 1971, Pianka 1971). The average size at reproduction was found to be 120 mm (females) and 127 mm (males) snout-vent length (Mayhew 1971). Clutch size can range from 3–8 eggs (Norris 1953). Once laid, the length of egg incubation ranges from 45–80 days until hatch (Krekorian 1984), and hatchlings are at least 47 mm snout-vent length before day seven (Parker 1972).

Generally an herbivore, the majority of Desert Iguanas’ diet is made up of plants, with insects contributing little overall dietary volume (Dibble et al. 2008). Examples of food items include leaves, seeds, and Cardon Cactus fruit (island populations), as well as ants, termites, and beetles (Grismer 2004, Dibble et al. 2008).

Desert Iguanas demonstrate a wariness for predators including escape behaviour into bushes and burrows, which can vary depending on the ambient temperature and also the speed of predator approach (Cooper Jr. 2003). Common predators include both birds (Revell 2005, Carbajal-Marquez et al. 2012) and snake species (e.g., Sidewinder; Avila-Villegas et al. 2007).

The Desert Iguana ranges widely in the southwestern United States, northwestern mainland Mexico, and the Baja Peninsula. Its range encompasses: southern Nevada; extreme southwestern Utah along the Virgin River in the vicinity of Beaver Dam Wash; northwest, central, and southern Arizona; southern California east of the Sierra Nevada and coast mountain ranges; southward into Mexico through northeastern Baja California, all of southern Baja California (excluding most of the Vizcaíno Desert), and western Sonora to northern Sinaloa. This lizard occurs on many islands in the Gulf of California and on Magdalena and Santa Margarita islands along the Pacific coast of Baja California, occurring most densely in sand habitats (Norris 1953, Hulse 1992, Grismer 2002, Stebbins 2003). The elevational range extends from below sea level in desert sinks (~ 40 m bsl) to about 1,520 m asl (Stebbins 2003).

Desert Iguanas are not protected by either United States or Mexican Law. They are found in protected areas in the United States, as well as the Gulf of California. Specifically, its range extends into several national parks and monuments, and federal wilderness areas (e.g., Mojave National Park, Joshua Tree National Monument, Anza Borrego Desert State Park, Kofa National Wildlife Refuge, Organ Pipe Cactus National Monument, Cabeza Prieta Wilderness, and Ironwood Forest National Monument). In Mexico, parts of the lizard's range is in the Bahía de Loreto National Park and the Área de Protección de Flora y Fauna Islas del Golfo de California which confers federal protection. The island populations are also included in the Gulf of California regional management plan for the protection of flora and fauna (Carabias Lillo et al. 2000), as well as a management plan for the Bahia de Loreto National Park (Bermúdez-Almada et al. 2002).

More research is needed concerning population sizes and trends, as well as threat assessment throughout the range. Particular regard should be given to the two different clades within the genus, as threats and protective areas vary spatially. Conservation measures may thus be relevant for subpopulations of the Desert Iguana.