The area was occupied by Native Americans as early as 100 BC, as indicated by the Portsmouth Earthworks, a ceremonial center built by the Ohio Hopewell culture between 100 and 500 AD.

[7]According to early 20th-century historian Charles Augustus Hanna, a Shawnee village was founded at the site of modern-day Portsmouth in late 1758, following the abandonment of Lower Shawneetown.

In 1796, Emanuel Traxler became the first person of European descent to permanently occupy land in what would later be known as Portsmouth, after the United States gained its independence.

Its residents, especially Joseph Love and Dan Lucas, provided aid to refugee slaves in the following years and assisted them in moving north.

[11] Although southern Ohio was dominated in number by anti-abolitionist settlers from the South, some whites also worked to improve conditions for blacks and aid refugee slaves.

Some found their future in Portsmouth; others moved north along the Scioto River to reach Detroit, Michigan, and get farther away from slave catchers.

After being elected to Congress, he wrote the Thirteenth Amendment to the United States Constitution, which abolished slavery in 1865 after the American Civil War.

Early industrial growth included having meat packing and shipping facilities for Thomas Worthington's Chillicothe farm, located north of Portsmouth on the Scioto River.

The construction of the Norfolk and Western (N&W) railyards beginning in 1838 and the completion of the Baltimore and Ohio Railroad (B&O) junction at the city in the late 1850s quickly surpassed the canal in stimulating growth.

[16] Such industrial and shipping growth greatly benefited Boneyfiddle (a west-end neighborhood in Portsmouth), where grand buildings were constructed with the wealth from the commerce.

In 1931, the Norfolk Southern Corporation built a grand, art deco passenger station at 16th and Findlay streets that provided a substantial entry to the city.

New investments and developments in the local economy led to Portsmouth's inclusion in Site Selection Magazine's "Top 10 Micropolitan areas".

[29] In January 2016, Portsmouth's plan, which emphasized using its most valuable asset, the Ohio River, as a key to revitalizing the city, earned it one of 15 spots in the competition's semifinals.

It is a midway point among four major cities: Charleston, West Virginia; Cincinnati and Columbus, Ohio; and Lexington, Kentucky, each of which is about 90 miles away (roughly a two-hour drive).

Graf Brothers Flooring and Lumber, the world's largest manufacturer of rift and quartered oak products, has two satellite log yards in Portsmouth, with the company's main office across the river in South Shore, Kentucky.

This work resulted in an exhibition at the Miami University Art Museum and a book, Portsmouth: Architecture in an Ohio River Town.

[45] The stadium opened in 1930 as the original home of the Portsmouth Spartans, now the fifth-oldest active franchise in the National Football League (as the Detroit Lions).

The Southern Ohio Museum, founded in 1979, has more than 60 exhibits, including artwork by Clarence Holbrook Carter and Jesse Stuart, China dolls, Native American artifacts, and works by local artists.

[47] In 1992 a nonprofit group headed by Louis R. and Ava Chaboudy was formed to investigate developing a mural-based tourist attraction on the floodwall.

[50] The murals cover subjects from the area's history from the ancient mound building Adena and Hopewell cultures to modern sporting events and notable natives.

In 1917, the construction of a dam downriver from Portsmouth meant that the rock would forever be submerged, if not for its recovery by a group of local divers led by an Ironton historian.

The Terrace Club's pool was still segregated despite the progress of the Civil Rights movement, which influenced Portsmouth's institutional makeup, as well as protests across the nation.

Early in that season, the Spartans competed in the first professional football night game, shutting out the visiting Brooklyn Dodgers 12–0 on September 24, 1930.

[60][61][62] Despite their on-field success, being based in the NFL's second-smallest city during the Great Depression meant the team was in constant financial trouble.

Revolutionary Championship Wrestling in Portsmouth has featured such stars as Big Van Vader, Jerry "The King" Lawler, Demolition Ax, "Beautiful" Bobby Eaton, "Wildcat" Chris Harris, and Ivan Koloff.

In May 2011, the Ohio Senate and House unanimously passed a bill cracking down on pill mills (signed into law by John Kasich) authored by Portsmouth's state representative Terry Johnson.

[71][72] Shortly thereafter, the DEA and state and local law enforcement agencies worked to identify and shut down a pharmacy and several doctors who had prescribed hundreds of thousands of opiates over a two-year period[73] by suspending their license to practice medicine.

In 1986, a legislative charter introduced by Vern Riffe to establish Shawnee State University was signed into law by Governor Richard Celeste.

[100] Portsmouth High School has an award-winning Interactive Media program that has won multiple awards for both video and graphic design.

Norfolk Southern operates a railyard and locomotive maintenance facility for its long-distance shipping route between the coalfields of West Virginia and points east, to the Great Lakes.