The Lawrence County Bank Building and Pierce City Fire Station, Courthouse and Jail are listed on the National Register of Historic Places.
Pierce City was laid out in 1870 as a stop on the Atlantic and Pacific Railroad. It was originally spelled Peirce City, named for Andrew Peirce, Jr. of Boston, president of the St. Louis–San Francisco Railway. The Pierce spelling was used erroneously by the United States Postal Service and adopted officially in the 1930s. A 1982 attempt to revert to Peirce was rejected by the United States Census Bureau.
In 1901 a white lynch mob killed several African Americans in Pierce City and the rest of the black community was forced at gunpoint to leave the town by its white citizens. This incident prompted Mark Twain to write the essay The United States of Lyncherdom. A 2007 PBS documentary, Banished, featured the incident.
One of the most notable tornadoes of the May 2003 tornado outbreak sequence was the one that hit in Pierce City. According to reports, nearly all of the buildings in the town were damaged, destroyed, or liable to collapse. Published and repeatedly broadcast reports of "all" or "nearly all" of the town's buildings sustaining severe damage were false. Approximately 90 percent of the historic downtown business district and homes nearby were severely damaged and later torn down. A nearby National Guard Armory, also known as the town's storm shelter in which several dozen people had fled to, sustained heavy damage, killing one person, J. Dale Taunton. Raging Winds... However, outside the main path of the tornado, many Pierce City structures, including homes and the Harold Bell Wright Museum sustained little or no damage.
The Pierce City tornado was an F-3 on the Fujita scale.