This aquatic species inhabits rocky, clear creeks and rivers that contain abundant cover in the form of large flat rocks, bedrock shelves, crevices, and logs (Green et al. 2014). It usually avoids water warmer than 20°C. Males prepare nests and attend eggs beneath large flat rocks or submerged logs. This species breeds by larval development. This is a long-lived species, with a life expectancy of 20–30 years (Peterson 1979, Taber et al. 1975, Wheeler et al. 2003). The generation length is estimated to be 10 years.

This species occurs across much of the interior portion of the eastern US, ranging from southern New York (Bishop 1941) to northeastern Mississippi and northern Alabama, including the Susquehanna River, tributaries of the Savannah River, the Tennessee River, and the Ohio River (Mount 1975, Green et al. 2014). This stretch encompasses southern Illinois (Smith 1961, Brandon and Ballard 1994, Phillips et al. 1999), southern Indiana (Minton 1972), Ohio (Pfingsten and Downs 1989) and Pennsylvania (McCoy 1982). They are also found in the Missouri River drainage, the Meramec River, and the White River in portions of Missouri and northern Arkansas (Johnson 1987, Trauth et al. 1992, Green et al. 2014). Their range extends into northern Georgia and the western portions of North Carolina and South Carolina (Martof et al. 1980) and into western Virginia (Tobey 1985) and West Virginia in areas west of the Allegheny Front (Green and Pauley 1987). They can also be found in extreme western Maryland. 

In Kentucky, near the centre of the range, Barbour (1971) regarded the species as most common in the upper reaches of the Cumberland, Kentucky, and Licking river systems. In Tennessee, no records exist for locations west of the Tennessee River (Redmond and Scott 1996). Collections are known from southeastern Kansas (Neosha River), but these are likely to have been from introduced individuals and not from a naturally occurring subpopulation (Collins 1982, 1993; W.H. Busby pers. comm.). There are early reports of this species from Iowa (Nickerson and Mays 1973b) however these records are uncertain. The species does not occur in Iowa today, and its historical occurrence is uncertain (Phillips and Humphries 2005). 

Previously reported historical records from the Great Lakes (Lake Erie) drainage, New Jersey, and Louisiana are probably erroneous (Pfingsten and Downs 1989, Harding 1997) and have therefore been excluded from the range map. Due to this species' secretive nature and its confusion with Necturus maculosus the present range is not known with certainty (Lannoo et al. 2005). Additionally, there is considerable taxonomic uncertainty surrounding this species. It is likely that there are several undescribed species contained within the current concept (T. Pierson pers. comm. June 2021).

Conservation Actions In-Place
This species is listed at the state level as "Endangered" in Illinois, Indiana, Maryland, and Ohio, as "Rare" in Georgia, and of "Special Concern" or a "Species of Concern" in New York, North Carolina, and Virginia. They are on the state Watch List in Missouri, and are considered in "Need of Maintenance" in Tennessee. Other states, including Alabama, Arkansas, Kentucky, Mississippi, South Carolina, and West Virginia track this species' distribution records in a database but do not generally afford them protection from take (Green et al. 2014). The subspecies Cryptobranchus alleganiensis alleganiensis and Cryptobranchus alleganiensis bishopi are listed at the federal level as "Endangered" under the Endangered Species Act.

Many of the presently known populations occur in national or state forests, national parks, and other public lands, where there is good potential for protecting habitat. However, some of these areas are still at risk of negative impacts from upstream activities in the watershed (NatureServe 2021). The St. Louis Zoo maintains a captive-breeding programme for this species.

In an effort to prevent the introduction of Bsal into the US, an Interim Rule of the Lacey Act has been enacted that bans the importation of 201 species of salamanders (USFWS 2016). Additionally, a temporary voluntary trade moratorium of imports of Asian salamander species that are known to carry the disease until such time as effective testing and treatment regimens can be developed and distributed has been recommended to all exporters, shippers, sellers and buyers by the Pet Industry Joint Advisory Council (PIJAC). A North America Bsal Task Force has also been created, with working groups designed to address a variety of disease prevention and mitigation goals (North America Bsal Task Force 2021).

Conservation Needed
The preservation of highly forested, low anthropogenically impacted catchments will be important to the conservation of this species (Wineland et al. 2018). Strengthened management and implementation of recovery plans on public lands would likely be helpful as well. 

Research Needed
Further taxonomic work is necessary to investigate this species complex and elucidate the taxonomic identity of its members. Population monitoring is also recommended given the widespread declines across its range and the likely future descriptions of cryptic species within this complex.