Hoxie is located approximately 120 miles northeast of Little Rock and 25 miles northwest of Jonesboro. Located in Lawrence County, the town that would eventually become Hoxie was created after the leaders of nearby Walnut Ridge could not agree on placement of a new railroad. The Kansas City, Springfield, and Memphis Railroad wanted to run the tracks through Walnut Ridge, but the town officials couldn't reach an agreement on where the rails should be placed. A local resident, Mary Boas, approached the railroad and offered the use of her land with no charge for the right-of-way. Construction of the railroad proceeded and the Boas family built a hotel near the railroad tracks.

Incorporated in 1888, the town was named Hoxie after a KCS&M railroad executive, Jack Hoxie. The new town continued to grow, in large part due to its location on the railroad, and by the early 1900s Hoxie was home to an ice plant, a bank, stockyards, a lumberyard, and a bottling company. The town suffered setbacks in 1923, when railroad shop workers went on strike, causing residents and railroad workers to relocate to larger cities to find jobs. In 1927, the KCS&M relocated to facilities to Poplar Bluff, Missouri.

Hoxie made national headlines when, in 1955, the Hoxie School District took steps to integrate the public schools. A reporter with the New York Times was in Hoxie and wrote stories on how the small Arkansas town was following the law of desegregation. Life magazine soon sent a photographer to document Hoxie's compliance with Supreme Court's ruling in Brown v. Board of Education of Topeka, Kansas. July 11, 1955, marked the first day of Hoxie's integration and the day was uneventful. However, after a photo essay appeared in the latest Life, in late July, things drastically changed.

Hoxie made the national headlines once again on Aug. 3, 1955, as over 300 local segregationists descended on the small town to protest the integration. They announced a boycott of the schools by white students. Ten days later, members of the Little Rock chapter of White America attended a segregation rally in Hoxie, at which a petition listing 1000 signatures was presented, demanding the resignation of the entire Hoxie School Board. Board members refused to resign and stood by their decision. Soon after, Arkansas governor Orval Faubus informed city officials that the state would not intervene in school district matters.

Vocal harassment by the segregationists continued for Hoxie's residents, both black and white. The Hoxie School Board finally took legal steps, filing a suit against the segregationists. The suit was appealed and was finally settled on Oct. 25, 1956, when the Eight Circuit Court of Appeals ruled in favor of Hoxie School Board.

Located in Lawrence County's Delta section, Hoxie's economy is tied very heavily to agriculture. Soybeans and rice are the main crops grown near Hoxie.

Hoxie is located less than three miles from Walnut Ridge, the county seat of Lawrence County. Nearby attractions include the Walnut Ridge Depot, the Walnut Ridge Army Flying School Museum, Rock ‘N' Roll Highway 67 Marker, Lake Charles State Park, and Powhatan Historic State Park.