This highly adaptable species can be found in almost all habitats in its range and reaches its greatest abundance in agricultural areas. They are almost exclusively nocturnal, becoming active shortly after sundown, foraging at various times during the night, and returning to their dens before daybreak. They do not hibernate, but they remain within their dens during especially cold weather. During these periods of inactivity, Striped Skunks use much of the body fat they accumulated during summer and autumn. Striped Skunks usually are solitary, but in winter communal denning of several females or of several females and one male are common. Striped Skunks excavate their own dens, but occupy dens dug by woodchucks, foxes, or badgers when available. Dens usually have one or two entrances to a single tunnel, and a nest area 0.5 to 1.5 m below the ground. Striped Skunks are not aggressive and generally seem oblivious to conspecifics and other animals. Threat postures and defensive behaviors are in response to being cornered by an intruder. Handstands and foot stamping result and, if the intruder persists, the skunks discharge their foul musk at the intruder. Skunks can hit human-sized targets at a distance of 6 m, but their accuracy is better at 3 m. The musk is an intense irritant to the eyes and acts as a depressant to the central nervous system.
Striped Skunks live as long as 10 years in captivity but rarely longer than 5 or 6 years in the wild.
Striped Skunks are insectivorous, but they are sufficiently opportunistic to take advantage of a great variety of other foods as they become available. These alternative foods include carrion, crayfish, small vertebrates, eggs of ground-nesting birds, fruits, and corn. About 80-90% of their diet is of animal origin.
Judging from all the dead skunks seen along roads, the greatest source of mortality almost certainly is automobiles. Farm equipment also take a toll. Predators that prey on Striped Skunks include Great-horned Owls, Cougars, Coyotes, badgers, foxes, and Bobcats. Mammalian predators generally leave skunks alone except when near starvation, but avian predators are not repelled by musk.
Striped Skunks breed in February and March. Females in estrous remain receptive until ovulation, which is induced by copulation. If a female does not become pregnant, she may enter estrous again in May. Gestation lasts from 59 to 77 days. Parturition usually occurs in May or early June. Litters range from 2 to 10 young and average 6 or 7. The kittens are born sparsely-haired with their eyes and ears closed. Their ears and eyes open about 3 or 4 weeks after birth. Their anal scent glands contain musk at birth, but kittens do not develop control of them until they are 2 or 3 weeks old. They begin to eat solid food at about 6 or 7 weeks, and they leave the den to forage with the female beginning at about 8 weeks. The kittens are weaned at 8 to 10 weeks, and disperse from the burrow when they are 12 to 14 weeks old, usually moving only a short distance to find a suitable denning site. Females are capable of breeding at 10 months of age.