The east-central community of Carlisle was founded on August 1, 1872 by Samuel McCormick but it did not become populated until rice was introduced into the area in 1886. Historians agree with the town's claim to being the birthplace of rice growing on the Grand Prairie. W.H. Fuller is credited with introducing rice to Carlisle.

There are two different stories regarding the naming of the town, according to local legend. One is that Samuel McCormick had lived in Carlisle, Pennsylvania, and named the town after his former home, while the other claims McCormick named the town after a close friend who was a senator from another state.

Historic accounts say Fuller went to Louisiana on a hunting trip in the summer of 1886. While there he took note of several rice farms and realized that the abundance of fast growing tall grass in the Grand Prairie left plenty of decaying plant matter needed to make the soil fertile for growing. He decided to try growing rice near his home. In 1903 Fuller returned to Louisiana and purchased rice seed along with constructions materials. Spring of 1904 brought the first planting with financial backing from the citizens of Carlisle and neighboring towns such as Hazen. The first crop produced 5,225 bushels of rice from 70 acres, demonstrating to area residents that there was money to be made from farming rice.

The John Morris farm also experimented with rice that year and became the site of the first irrigation system ever used in Arkansas. This important discovery had a significant impact on the rice industry in the region. The first rice mill in town was constructed in 1908 by the Carlisle Rice Milling Company. When built, it was the largest rice mill in the state. The company became the Arkansas State Rice Milling Company in 1916 and then Riviana Foods, Inc. in 1965. The company remains a nationwide rice producer.

The railroad also played an important in Carlisle's history. The Memphis and Little Rock railroad which ran through the heart of town was completed in 1858. The tracks were destroyed during the Civil War and rebuilt during Reconstruction, providing an economical way to transport rice and receive other products. The Old Military Road from Memphis to Little Rock is just north of the city. It was used as a part of the Trail of Tears during the forced removal of Native Americans in the 1830s. It was also used by Union and Confederate soldiers during the Civil War.  The Trail of Tears, along with other historically significant routes, is now part of the Arkansas Heritage Trails System.

The community boasts two Works Progress Administration projects – the first library and a gymnasium which today serves as a community center.

Today rice farming is still the mainstay of the community but it has diversified into soybean and cotton farming as well. It is the birthplace of Maurice “Footsie” Britt, a World War II hero who was the first soldier to win the four top medals for valor, including the Congressional Medal of Honor. He later served as Lieutenant Governor under Winthrop Rockefeller from 1967 to 1970.

Carlisle is located in Lonoke County approximately 35 miles from Little Rock.