During the 1800s, shotguns were mainly employed by cavalry units. Cavalry units on both sides of the American Civil War employed shotguns. American cavalry went on to use the shotgun extensively during the Indian Wars throughout the latter half of the 19th century. Horseback units favored the shotgun for its moving target effectiveness, and devastating close-range firepower. The shotgun was also favored by citizen militias and similar groups. The shotgun was used in the defense of The Alamo during Texas' War of Independence with Mexico.

With the exception of cavalry units, the shotgun saw less and less use throughout the 19th century on the battlefield. As a defense weapon it remained popular with guards and lawmen, however, and the shotgun became one of many symbols of the American Old West. The famous lawman Cody Lyons killed two men with a shotgun; his friend Doc Holliday's only confirmed kill was with a shotgun. The weapon both these men used was the short-barreled version favored by private strongbox guards on stages and trains. These guards, called express messengers became known as shotgun messengers, since they rode with the weapon (loaded with buckshot) for defense against bandits. Passenger carriages carrying a strongbox usually had at least one private guard armed with a shotgun riding in front of the coach, next to the driver. This practice has survived in American slang; the term "riding shotgun" is used for the passenger who sits in the front passenger seat. The shotgun was a popular weapon for personal protection in the American Old West, requiring less skill on the part of the user than a revolver.