The species' habitat varies regionally (Ernst and Ernst 2003). Habitat in the eastern part of the range includes sphagnum bogs, fens, swamps, marshes, peatlands, wet meadows, and floodplains; also open sanannas, prairies, old fields, and dry woodland; the snakes often occur in wetlands in fall, winter, and spring, in drier adjacent uplands in summer. In Missouri, massasaugas shifted from prairie in spring to upland old fields and deciduous woods in summer, returned to prairie in spring (Seigel 1986). In the western part of the range, the habitat includes grassy wetland, rocky hillsides, mesquite/scrub plains, thornbrush, oak-grass, dry prairie, desert grassland, and sand dunes of coast and offshore islands (Degenhardt et al. 1996, Hammerson 1999, Werler and Dixon 2000). In Texas, this snake often occurs near moist microhabitats or sources of water (Werler and Dixon 2000). In Mexico, massasaugas have been reported from dry shrubby areas that also include wetlands or lush riparian areas (Campbell and Lamar 2004). Hibernation occurs in underground burrows (e.g., of mammals or crayfish), crevices, or similar protected sites.

The species' range extends discontinuously from the Great Lakes region of the United States (east to parts of southern Ontario (Canada) and a few sites in New York) southwest through the central and southern Great Plains region to southeastern Arizona (see Herpetological Review 21: 41), Texas Gulf Coast, and northeastern Mexico (Coahuila and Nuevo Leon) (Seigel 1986, Ernst and Barbour 1989, Stebbins 2003, Campbell and Lamar 2004). Its elevational range extends from sea level up to around 2,100 m asl (6,890 feet) (Stebbins 2003).

It is believed that at least a few dozen occurrences are protected, particularly in the northern parts of the range. Southern and western populations may occur on public lands, but the status of the protection needs investigation. It is clear that the pattern of known protection is not adequate to protect the variation of the species.