In 1900, the L&N Railroad won the right to establish the railroad through this area. The town is named for Henry Opp, who represented L&N in successful legal negotiations. The coming of the railroad consolidated the surrounding areas and brought people and businesses from Poley, Opine, Cool Springs and other nearby areas. The first depot was a railcar parked on a sidetrack. As the town developed, a wooden building was constructed. The present structure was constructed in 1928 after the first building burned. The town received its charter from the state Legislature on February 28, 1901 and was officially incorporated on July 12, 1902 with limits extending one mile each way from the L&N Depot.
Opp has become known as "The City of Opportunity." The railroad was attracted to this area because of the huge virgin pine forests and the available lumber. This spot located on high ground proved to be an excellent turning point with one branch turning south toward Florala and another east to Geneva. The abundance of pine trees also attracted Opp's first industry, naval stores. Turpentine resin was harvested from pines growing on what is now the main thoroughfares of Opp. However, as the trees were cut for timber and the land cleared for farming, the naval stores were eliminated. City leaders looking for new industry were led to a cotton mill. Opp Cotton Mill was incorporated in 1920, and three years later Micolas Cotton Mill was added. In the years that followed WWII, the "cut and sew" industry provided many jobs for Opp's citizens. As the 20th century came to an end, textiles left the south for other parts of the world. As the 21st century began, Opp moved into the age of space and technology.