Ordinarily, cemeteries, birthplaces, or graves of historical figures, properties owned by religious institutions or used for religious purposes, structures that have been moved from their original locations, reconstructed historic buildings, properties primarily commemorative in nature, and properties that have achieved significance within the past 50 years shall not be considered eligible for the National Register. However, such properties will qualify if they are integral parts of districts that do meet the criteria or if they fall within the following categories: 

A. a religious property deriving primary significance from architectural or artistic distinction or historical importance; or 

B. a building or structure removed from its original location but which is significant primarily for architectural value, or which is the surviving structure most importantly associated with a historic person or event; or 

C. a birthplace or grave of a historical figure of outstanding importance if there is no other appropriate site or building directly associated with his or her productive life; or 

D. a cemetery that derives its primary significance from graves of persons of transcendent importance, from age, from distinctive design features, or from association with historic events; or 

E. a reconstructed building when accurately executed in a suitable environment and presented in a dignified manner as part of a restoration master plan, and when no other building or structure with the same association has survived; or 

F. a property primarily commemorative in intent if design, age, tradition, or symbolic value has invested it with its own historical significance; or 

G. a property achieving significance within the past 50 years if it is of exceptional importance.

The two principal issues to consider in determining eligibility for the National Register are "significance" and "integrity." 

A property may have "significance" for association with important events or patterns of history (criterion A); for association with an important historical figure (criterion B); as an important example of period architecture, landscape, or engineering (criterion C); or for the information it is likely to yield (criterion D, applied to archaeological sites and districts, and sometimes applied to certain types of structures). A National Register nomination must demonstrate how a property is significant in at least one of these four areas. For properties nominated under criterion A, frequently cited areas of significance are agriculture, community planning and development, social history, commerce, industry, politics and government, education, recreation and culture, and others. For technical reasons, criterion B (significant person) nominations are rare. Criterion C (architecture) is cited for most, but not all, nominations of historic buildings. Archaeological sites are always nominated under criterion D, but may also have significance under one or more of the other three criteria. 

Properties are nominated at a local, state, or national level of significance depending on the geographical range of the importance of a property and its associations. The level of significance must be justified in the nomination. The majority of properties (about 70%) are listed at the local level of significance. The level of significance has no effect on the protections or benefits of listing. 

Besides meeting one or more of the above criteria, a property must also have "integrity" of "location, design, setting, materials, workmanship, feeling, and association." This means that the property must retain enough of its historic physical character (or in the case of archaeological sites, intact archaeological features) to represent its historic period and associations adequately. 

All properties change over time, and in some cases, past alterations can take on historical significance in their own right. The degree to which more recent, incompatible, or non-historic alterations are acceptable depends on the type of property, its rarity, and its period and area of significance. Buildings with certain types of alterations are usually turned down by the National Register Advisory Committee. For example, 19th and early 20th century wood frame buildings that have been brick veneered in the mid-20th century are routinely turned down for loss of historic integrity. Similarly, it is extremely rare that buildings covered in synthetic materials such as aluminum or vinyl siding are individually eligible for listing in the Register.

The criteria exclude birthplaces and graves of historical figures, cemeteries, religious properties, moved buildings, reconstructions, commemorative properties, and properties less than 50 years old, with certain exceptions. The following exceptions are sometimes encountered: 

Historic churches that are architecturally significant and retain sufficient architectural integrity can be successfully nominated under criterion C (architecture), sometimes together with criterion A for social or religious history, provided they have not been brick-veneered or covered in aluminum or vinyl siding. 

Cemeteries may sometimes successfully be nominated under criterion C when they retain important examples of historic stone carving, funerary art, and/or landscaping, and they also may be eligible under criterion A or criterion D. However, both the National Register Advisory Committee and the National Register have turned down nominations of graves when the historical importance of the deceased is the sole basis for the nomination. The National Register was created primarily to recognize and protect historic places and environments that represent how people lived, worked, and built in the historic past. Human burials are recognized and protected under other laws and programs. 

Moved buildings may sometimes be successfully nominated under criterion C for architecture when they remain in their historic communities and the new setting adequately replicates the original setting. The point to remember is that the program is called the National Register of Historic Places, not Historic Buildings or Historic Things, because significance is embodied in locations and settings as well as in the structures themselves. Buildings moved great distances, buildings moved into incompatible settings (such as a farmhouse moved into an urban neighborhood or a downtown residence moved to a suburb), and collections of buildings moved from various locations to create a pseudo-historic "village" are routinely turned down. In some cases, the relocation of a historic building to a distant or incompatible setting may be the last and only way to save it, and such an undertaking may be worthwhile. However, sponsors of such a project must understand that the property subsequently may not be eligible for the National Register. 

If a property is less than 50 years old, it can be nominated only if a strong argument can be made for exceptional significance. For example, Dorton Arena on the State Fairgrounds was completed in 1953. It was successfully nominated to the National Register in 1973 as one of the most important examples of modernism in post-World War II American architecture.