Cabell Huntington Hospital, one of the 10 largest general hospitals in West Virginia, is named after the county and city that financed its initial construction with taxpayers' money.

Community leaders in Huntington and Cabell County decided in 1945 that there was a critical need for a new acute care hospital and convinced the state legislature to approve a bill to authorize a city county hospital. Voters in both the city and the county approved a $3 million bond issue in 1952, and construction soon began on the site of a former brickyard. The facility first opened for business in 1956. Community response was so great that a three-phase expansion program was begun soon afterward. Cabell Huntington was originally a 236-bed hospital, but the first phase of the expansion increased the size to 280 beds and 48 bassinets in 1963, followed by a second expansion in 1976 that added more beds as well as expanded emergency room space, laboratory facilities, the cafeteria and business offices. A third phase of expansion was initiated after approval of a $9 million bond issue that included a 26-bed critical care floor that opened in August of 1981. The region's only birthing room and a high-risk labor room were part of the expansion in 1981 and 1982. The hospital has the only burn unit in the state, treating electrical and chemical burns as well as those caused by fire.

In 1989, construction began on a $12 million surgery suite addition, and in 1998 the new partnership with the Marshall University School of Medicine produced the most significant expansion of the physical plant. This new MU Medical Center, connected to the existing hospital, brings all of the School of Medicine physicians, faculty, and students together in one location.

The Edwards Comprehensive Cancer Center opened in 2006,specializing in cancer care for both children adults. The Hoops Family Children's Hospital opened in 2012. It's a 72-bed "hospital within a hospital," located on Cabell Huntington's fifth floor. In 2017, Cabell Huntington introduced its Institute for Minimally Invasive Surgery.

The hospital is governed by a board of directors, representing a wide range of community interests, including labor and business. The board appoints the medical and dental staff, composed of approximately 325 physicians and dentists in the community. In 1985, the hospital began converting from a public nonprofit corporation to a private nonprofit corporation. In early 1988, this conversion was completed and Cabell Huntington Hospital, Inc., became the new corporation governing and overseeing Cabell Huntington Hospital.

Plans to merge operations with St. Mary's Hospital of Huntington and Pleasant Valley Hospital in Point Pleasant were completed in 1998 when the West Virginia Health Care Authority approved a certificate of need for the creation of the new Genesis Health Care Services, Inc. The short-lived combination lasted until late 2001, when Genesis was dissolved. leaving Cabell Huntington to operate independently.

In 2007, the hospital opened the eight-story North Patient Tower and expanded its capacity once again. The hospital now has 313 beds.

In 2014, Cabell Huntington announced it planned to acquire St. Mary’s Medical Center. The Federal Trade Commission filed an administrative complaint against the merger in November 2015, citing concerns over health care costs and quality. In 2016, the Health Care Authority granted the hospital a certificate of need for the purchase. In January 2018 all parties reached a compromise and objections to the merger were withdrawn. In March, the Vatican approved the transfer of sponsorship to Cabell Huntington. St. Mary’s retains its name and Catholic affiliation, and the two hospitals will be unified under a single healthcare system.