Founded in 1831, the city was originally known as Boardtown for the local sawmilling operation there, but was renamed in 1837 to honor American Revolutionary War general John Stark.

The university was located near Starkville in the Mississippi Black Belt due to the region's agricultural productivity, particularly in the timber, cattle, and dairying industries.

The Cotton District, developed in the 1960s as North America's first New Urbanist community, is an active student quarter located between downtown Starkville and the university campus.

Artifacts in the form of clay pot fragments and artwork dating from that time period have been found east of Starkville at the Herman Mound and Village site, which is listed on the National Register of Historic Places.

The earthwork mounds were made by early Native Americans of moundbuilder cultures as part of their religious and political cosmology.

Shortly before the American Revolutionary War period, the area was inhabited by the Choccuma (or Chakchiuma) tribe.

White settlers were drawn to the Starkville area because of two large springs near the old part of the town, which Native Americans had used for thousands of years.

[11] In 1865, during reconstruction, the officer in charge of Starkville allowed a black man accused of raping a white girl to be lynched by running him down with hounds.

[11] A yellow fever epidemic in 1898 resulted in a quarantine of Starkville's railroads by the towns of West Point, Columbus, Artesia and Kosciusko.

[17] Before the Civil War, Colonel Montgomery imported cattle from the isle of Jersey, initiating the areas prominence as a dairy center.

[11] In April 1912, Gabe (sometimes reported as Abe) Coleman, an African-American man was accused of attacking a farmer's wife and was shot to death by a mob.

They were met at a bridge near the A & M dairy barn by white men from Starkville and West Point armed with cannon loaded with buckshot and iron.

[20] In 1915, two African-American men, Dit Seals and Peter Bolen,[21] were hanged in a public execution while a crowd of 5,000, including blacks and whites, and children watched and sang There is a Land of Pure Delight.

The story was widely reported as a "gala hanging" sponsored by the merchants of Starkville by various newspapers including the New York World and Chicago Tribune, while the Detroit Times described it as little better than a lynching.

[26] On March 21, 2006, Starkville became the first city in Mississippi to adopt a smoking ban for indoor public places, including restaurants and bars.

[27] In February 2018, Starkville denied a local LGBTQ organization a permit to host a pride parade.

Faculty, staff and students at Mississippi State University, including those from other nations, have greatly increased the city's diversity.

[42] The architecture of the Cotton District has historical elements and scale, with Greek Revival mixed with Classical or Victorian.

The Starkville-Oktibbeha County Public Library System is headquartered at its main branch in Downtown Starkville.

Executive and legislative authority in the city of Starkville is respectively vested in a mayor and seven-member board of aldermen concurrently elected to four-year terms.

Starkville has a strong-mayor government, with the mayor having the power to appoint city officials and veto decisions by the board of aldermen.

Starkville is split between Mississippi House districts 38 and 43,[45] currently represented by Democrat Cheikh Taylor and Republican Rob Roberson.

The city is similarly split between Mississippi Senate districts 15 and 16 represented by Republican Bart Williams[46] and Democrat Angela Turner-Ford.

[50] As a result of this disparity in the racial demographics of the two districts, Oktibbeha County was placed under a Federal desegregation order.

The school will be for all grade 6 and 7 students in Oktibbeha County and will be located on the Mississippi State University campus.

[64] Pilot Charles Lindbergh, the first to fly solo across the Atlantic Ocean, made a successful landing on the outskirts of Starkville in 1927 during his Guggenheim Tour.

"[111] In 2021, a Mississippi Country Music Trail marker honoring Cash was installed in Starkville near the Oktibbeha County Jail.