国家人类基因组研究所最初是国家人类基因组研究中心（NCHGR），成立于1989年，旨在履行美国国立卫生研究院（NIH）在国际人类基因组计划（HGP）中的作用。HGP是与美国能源部合作开发的，于1990年开始绘制人类基因组图谱。

1993年，NCHGR通过建立校内研究部门将其在NIH校园中的作用扩大到将基因组技术应用于特定疾病的研究。1996年，还成立了遗传性疾病研究中心（CIDR）（由八个NIH研究所和中心共同资助），以研究复杂疾病的遗传成分。

1997年，美国卫生与公众服务部将NCHGR更名为国家人类基因组研究所（NHGRI），正式将其提升为研究机构的地位 - 组成NIH的27个研究所和中心之一。现在，随着人类基因组序列自2003年4月完成以来，世界各地的科学家都可以访问一个数据库，该数据库极大地促进和加快了生物医学研究的步伐。

The National Human Genome Research Institute was originally the National Center for Human Genome Research (NCHGR), established in 1989 to fulfill the role of the National Institutes of Health (NIH) in the International Human Genome Project (HGP). HGP, developed in collaboration with the US Department of Energy, began mapping the human genome in 1990.

In 1993, NCHGR expanded its role on the NIH campus to include the application of genomic technologies to disease-specific research by establishing an on-campus research unit. In 1996, the Center for Research in Genetic Diseases (CIDR) (co-funded by eight NIH institutes and centers) was also established to study the genetic components of complex diseases.

In 1997, the U.S. Department of Health and Human Services renamed NCHGR to the National Human Genome Research Institute (NHGRI), officially elevating it to the status of a research institution - one of the 27 institutes and centers that make up NIH. Now, with the completion of the human genome sequence in April 2003, scientists around the world have access to a database that has greatly facilitated and accelerated the pace of biomedical research.