Piggott is located approximately 180 miles northeast of Little Rock and 110 miles north of West Memphis and is along the Crowley's Ridge Parkway National Scenic Byway in Clay County. Originally known as Huston, the town was renamed Piggott after one of the early settlers, Dr. James Piggott. Dr. Piggott was instrumental in getting a post office established in the community.

Piggott is also located along Davidson's Approach, a movement of U.S. General John Wynn Davidson's troops during the 1863 Little Rock Campaign, and U.S. General Frederick Steele's movement during the second phase of the Pea Ridge Campaign. These along with other historic Civil War routes and significant movements, such as the Trail of Tears and the Southwest Trail, are now part of the Arkansas Heritage Trails System.

In June 1913, Paul and Mary Pfeiffer moved to Piggott from St. Louis and eventually amassed 63,000 acres in Clay County. Their oldest daughter Pauline met and later married writer Ernest Hemingway. They visited the home frequently during their marriage (1927-1940) and the Pfeiffers converted a barn behind the home into a studio for Hemingway's use during his stays. It was here that Hemingway wrote a large portion of one of his most famous novels, A Farewell to Arms, and various short stories. The home stayed in the Pfeiffer family until 1950 when Mary Pfeiffer died. In 1982, the Pfeiffer Home and Carriage House were listed in the National Register of Historic Places. Arkansas State University purchased the historic property in 1997, restored it to the time period when Hemingway visited, and opened the property as the Hemingway-Pfeiffer Museum and Educational Center.

In August 1956, Piggott was chosen as one of the filming locations for A Face in the Crowd, a motion picture starring newcomers Andy Griffith and Lee Remick. Local residents appeared in the movie as extras. Scenes were shot at the local football field, the courthouse and at the home of Pauline Pfeiffer's brother, Karl. The movie, directed by Elia Kazan, was premiered in Piggott in May 1957. Piggott is also home to the Matilda and Karl Pfeiffer Museum and Study Center. Located in the Pfeiffer's 1933 Tudor Revival home, the museum features more than 1400 mineral specimens that Matilda Pfeiffer collected over her lifetime. The house grounds serve as a preserve for native Arkansas plants. In the fall, nearby Pumpkin Hollow attracts visitors from miles around with its corn mazes, haunted barn and forest, hay slides and gourds and pumpkins grown on the premises.