Located on the Ohio River near where West Virginia, Kentucky, and Ohio meet, the city of Huntington was founded in 1871 by railroad mogul Collis P. Huntington as the western terminus of his Chesapeake & Ohio (C&O) Railway. Seeking a convenient spot to transfer cargo and passengers between the C&O and the Ohio's riverboats, he selected Holderby's Landing, a stretch of farmland just downstream from the mouth of the Guyandotte River.

Huntington directed his brother-in-law, Col. Delos W. Emmons, to purchase 21 farms totaling 5,000 acres. Rufus Cook, a Boston civil engineer, was hired to design a town plan featuring a geometric gridwork of intersecting avenues and streets, consecutively numbered so that any address would be easy to find. On February 27, 1871, the West Virginia legislature approved an act incorporating the new city, named for its founder. On December 31 of that year, Peter Cline Buffington was elected Huntington's first mayor. The community grew rapidly and by the early 1890s had a population of more than 10,000. In 1887, after considerable controversy, the seat of Cabell County was moved from Barboursville to Huntington.

In selecting a site for his new city, Huntington chose well. The community prospered as a gateway to the coalfields of southern West Virginia. Coal flowed to market via Huntington, and manufactured goods traveled the other direction, a two-way traffic that spawned thousands of jobs in the river city. In addition to its role as a transportation hub and a center of retail and wholesale trade, Huntington also attracted manufacturers who produced a broad array of products, including rail cars, steel, glass, china, brick, stoves, furniture, and even church pews.

Organized in June of 1872, the First Congregational Church is said to be the city's oldest church. Huntington today is home to more than 130 congregations, representing virtually every faith. That includes seven congregations located in a six-block stretch of downtown Fifth Avenue.

Huntington is also known for its broad, tree-lined streets; for Ritter Park, fashioned in 1913 from land originally intended for use as a city incinerator; for the grand Keith-Albee Theater, which has welcomed moviegoers since 1928; for the handsome Cabell County Courthouse, dedicated in 1901; and for Heritage Village, with its many historic buildings.

Huntington is home to Marshall University. Older than the city itself, Marshall was established in a log church at its present location in 1837. Marshall has grown steadily over the years, especially since it became a university in 1961. Today, it boasts some 12,000 undergraduate and graduate students, enrolled in a broad range of academic programs. Marshall's sports teams are a source of community-wide pride. And its Joan C. Edwards School of Medicine, which admitted its first class in 1978, has helped make the city a regional health care center.

Flooding was a serious problem in Huntington for many years. Serious floods occurred in 1884 and 1913, but the worst occurred on January 28, 1937, when the river inundated much of Huntington. The river crested at a record 69.45 feet, more than 19 feet above flood stage. Following the disastrous flood, the U.S. Army Corp of Engineers constructed an 11-mile floodwall to protect the city from future floods. Unfortunately, the wall also prompted the city to forget its historic ties with the river. That was corrected in 1984, with the opening of the David W. Harris Riverfront Park.

The 1950s were years of remarkable growth and achievement for Huntington, the city's zenith, some would argue. The decade saw construction of Tri-State Airport, the Huntington Museum of Art, Cabell Huntington Hospital, and Veterans Memorial Field House. In the decades following, Huntington saw many factories close, businesses slump, and jobs disappear, including the closing of the CSX Huntington Division in 2016. Part of the decline stemmed from sweeping cutbacks in coal mine employment as automation took hold in the surrounding coalfields, part was attributable to the same "rust belt" phenomenon experienced by so many of the nation's other cities. Some felt the 1950s decision to route Interstate 64 outside Huntington was a mistake, and the later building of Huntington Mall far to the east clearly hurt downtown business. The city's economic woes were reflected in a dramatic population decline. Huntington lost nearly 35,000 residents from 1950 to 2000, leaving a population of 51,475. The city’s population was 46,842 in 2020. Some residents simply moved to growing suburban areas outside the city, but many left the region, seeking better opportunities elsewhere.

In 1993, more than 600 employees lost their jobs when the Owens Brockway glass container plant, a fixture in the city for 80 years, closed. Stung by that closing, nearly 1,000 concerned residents braved a snowstorm to attend a public forum focusing on the city's future. From that meeting was born a new public-private partnership, dubbed Our Jobs, Our Children, Our Future. As part of that economic development effort, the closed Owens Brockway plant was purchased and turned into an industrial park. And the same public-private partnership attracted more than 2,000 jobs in information services, establishing telemarketing and market research as important elements in the Huntington economy. Pullman Square, a downtown development project combining entertainment and business establishments, opened in 2004.