The gray fox is mainly distinguished from most other canids by its grizzled upper parts, black-tipped tail and strong neck, while the skull can be easily distinguished from all other North American canids by its widely separated temporal ridges that form a U-shape. There is little sexual dimorphism, save for the females being slightly smaller than males. The gray fox ranges from 76 to 112.5 cm (29.9 to 44.3 in) in total length. The tail measures 27.5 to 44.3 cm (10.8 to 17.4 in) of that length and its hind feet measure 100 to 150 mm (3.9 to 5.9 in). The gray fox typically weighs 3.6 to 7 kg (7.9 to 15.4 lb), though exceptionally can weigh as much as 9 kg (20 lb). It is readily differentiated from the red fox by the lack of "black stockings" that stand out on the latter and the stripe of black hair that runs along the middle of the tail. In contrast to all Vulpes and related (Arctic and fennec) foxes, the gray fox has oval (instead of slit-like) pupils.

The gray fox's ability to climb trees is shared only with the Asian raccoon dog among canids. Its strong, hooked claws allow it to scramble up trees to escape many predators, such as the domestic dog or the coyote, or to reach tree-bound or arboreal food sources. It can climb branchless, vertical trunks to heights of 18 meters and jump from branch to branch. It descends primarily by jumping from branch to branch, or by descending slowly backwards as a domestic cat would do. The gray fox is nocturnal or crepuscular and makes its den in hollow trees, stumps or appropriated burrows during the day. Such gray fox tree dens may be located 30 ft above the ground. Prior to European colonization of North America, the red fox was found primarily in boreal forest and the gray fox in deciduous forest, but now the red fox is dominant in most of the eastern United States since they are the more adaptable species to development and urbanization. In areas where both red and gray foxes exist, the gray fox is dominant.