Black-footed Ferret is limited to open habitat, the same habitat used by prairie-dogs Cynomys: grasslands, steppe and shrub steppe. It depends largely on prairie-dogs, preying on them and using their burrows for shelter and denning (Hillman and Clark 1980). Ferret habitat selection at fine scales is dependent on density of prairie-dog burrow openings (Eads et al. 2011, 2013). It has been estimated that about 40-60 hectares of prairie-dog colony are needed to support one Black-footed Ferret. Ayers et al. (2014) found that Black-footed Ferrets successfully recruited offspring with prairie-dog densities of at least 12 individuals/ha in ferret core areas. Biggins et al. (1993, 2006) provided information on evaluating areas as potential Black-footed Ferret habitat; factors include size of prairie-dog complex, prairie-dog population density, spatial arrangement of prairie-dog colonies, potential for disease in prairie-dogs and in ferrets, potential for prairie-dog expansion, abundance of predators, future resource conflicts and ownership stability, and public and landowner attitudes.

Historically, Black-footed Ferret was found throughout the Great Plains, mountain basins, and semiarid grasslands of west-central North America, from southern Canada to northern Mexico wherever its prey, prairie-dogs Cynomys, were located (Hillman and Clark 1980). This species was extirpated from most of its former range mainly as a result of prairie-dog control programmes and sylvatic plague - an exotic disease which was introduced to the wild population. Today, it occurs in the wild as 17-22 reintroduction efforts, only four of which are self-sustaining. These four are in South Dakota, Wyoming and Arizona (all USA), and have a combined range exceeding 500 km². There are four populations of limited success in Kansas, New Mexico, South Dakota and Utah, USA; six populations of recent initiation in Arizona, Colorado and  Montana (all USA); two populations in Canada and Mexico which are now again extirpated; and six declining or extirpated populations in Colorado, Montana, New Mexico and South Dakota (all USA).

It has been recorded from 500 to 3,100 m asl.

The Black-footed Ferret captive breeding programme was initiated in October 1985 by the Wyoming Game and Fish Department in cooperation with the United States Fish and Wildlife Service. Eighteen Black-footed Ferrets were captured between 1985 and 1987 from the last-known population, in Wyoming, to start a captive breeding population (Miller et al. 1996), with the ultimate goal of reintroduction.

Because of relatedness among many of the 18 Ferrets captured, genetic contributions equate to no more than seven founder equivalents. As of 2008, there are six institutions (one federal facility and five zoos) participating in the propagation programme under the supervision of the United States Fish and Wildlife Service. Beginning in 1985, more than 8,000 Black-footed Ferrets have been born in captivity, with 323 kits weaned in 2014. Beginning in 1991, Ferrets have been reintroduced at sites in eight Western U.S. states (Montana, South Dakota, Wyoming, Colorado, Utah, Arizona, Kansas and New Mexico), one site in Mexico (Bard 2002, Bronson et al. 2007) and one site in Canada. In 2014 alone, 202 kits were released at nine separate reintroduction sites..

The species is listed on CITES Appendix I and is listed under the U.S. Endangered Species Act.