In the northeast, this species inhabits mountainous or hilly deciduous or mixed deciduous-coniferous forest, often with rocky outcroppings, steep ledges, and rock slides (Petersen and Fritsch 1986, Brown 1993). In the upper midwest, this snake occurs on steep rocky bluffs and bluff prairies with oaks (Breckenridge 1944, Oldfield and Keyler 1989, Vogt 1981). In the central midwest, optimum habitat is a high, dry ridge with oak-hickory forest interspersed with open areas (Minton 1972), and "deciduous forest, especially along hilltop rock outcrops in thick woods" (Fitch 1958). In the south, preferred habitat is "hardwood forests of the type found in Loess Bluff and in many river bottoms" (Cook 1943), swampy areas and floodplains (Mount 1975), wet pine flatwoods, river bottoms and hydric hammocks (Ashton and Ashton 1981), and hardwood forests and cane fields of alluvial plain and hill country (Dundee and Rossman 1989). Fogell et al. (2002) documented a relatively high level of agricultural field use at the western edge of the range in Nebraska. Activity is primarily terrestrial, but timber rattlesnakes sometimes climb into vegetation (see Fogell et al. (2002). Hibernacula are typically located in a rocky area where underground crevices provide retreats for overwintering, such as a fissure in a ledge, a crevice between ledge and ground, talus (rock slide) below a cliff, open skree slope (fallen rocks not associated with a cliff), or fallen rock (talus or skree) partly covered by soil (Martin 1989). At least in the northeastern part of the range (Reinert 1984, Reinert and Zappalorti 1988, Hammerson and Lemieux 2001), males and non-gravid females are primarily forest dwellers and gravid females use open, sparsely forested sites. Similarly, in Wisconsin Keenlyne (1972) reported gravid females using flat slab rocks and grassy, open slopes. This open habitat was not used by males or nongravid females. "Transient habitat" a somewhat arbitrary category, generally is within 200 m of a den. It tends to be broken by the rough topography and rocky terrain near the den site and supports more open woodland with exposed clearings and shelter rocks. This habitat occurs on outcrop knolls (Brown 1989) used as "stop-over" basking locations by rattlesnakes migrating away from a den in spring. This habitat also is used by gravid females during their reproductive year.

This species ranges widely in the United States, ranging marginally into southern Canada (where it is extinct). Its range extends from central New England to northern Florida, and west to eastern Texas, central Oklahoma, eastern Kansas, southeastern Nebraska, southern and eastern Iowa, and southeastern Minnesota (Martin, in Tyning 1992; Ernst and Ernst 2003; Campbell and Lamar 2004). The distribution is spotty along the western and northern edges of the range. Sizeable populations still occur in the Appalachian Mountains from Pennsylvania though the Virginias, across eastern Kentucky and Tennessee to northeastern Alabama, in the Ouachita and Boston mountains of Arkansas and extreme eastern Oklahoma, in heavily wooded sections of the southeastern Coastal Plain from North Carolina to northeastern Florida and west to Louisiana and southern Arkansas, and in the Piedmont in the Uwharrie National Forest of central North Carolina and Pine Mountain of west-central Georgia (Martin in Tyning 1992). See Martin (in Tyning 1992) for a detailed range map and further details on current known distribution. Dens occur at elevations of up to about 5,000 feet in the southern Appalachians, 2,200 feet in southern New England, and about 1,300 ft in northeastern New York, Wisconsin, and Minnesota; individuals may range to higher elevations in summer (Martin in Tyning 1992).

At least several occurrences are protected. Protection needs: 1) protect all known denning areas and adequate surrounding foraging habitat (generally a radius of about 1.5 to 2.5 miles from the den site) (see Brown 1993); 2) foster protection through public education; and 3) do not reveal den locations to the general public or unknown persons.