In the late 1700s and 1800s, horse and ox-drawn covered wagons from Charleston, Savannah, and Jacksonville, creaked and groaned across the South as pioneer families searched for a place to build new homes and to start a new life. Those pioneers who passed through the vast pine forests in the southeast corner of the territory that was to later become the state of Alabama would often stop at a spring known as Poplar Head, where they would camp for a while and rest. Most of those early travelers believed that the sandy soil which nurtured the thick pine forests would not be suitable for farming, so they moved on.

Poplar Head, named for the poplar trees that encircled the glade where the cool water, or "head" (as springs were often called) welled from the earth, was where ancient Indian trails met, crossed, and then continued on. The glade where the spring was located was often used by Indians from the various tribes of the Creek Confederacy as a meeting place and as a campground. In the 1830s a fort existed on the Barber Plantation, ten or twelve miles east of Poplar Head, where the settlers from the surrounding town and hamlets could go when they felt threatened by the Indians. By 1840 the Indian wars in Alabama were over and the fort soon disappeared.

By 1885, the hamlet had grown into a village. The new settlers realized that if the community's growth was to be sustained they needed a governing body and local law enforcement. On November 10, 1885, the people of Poplar Head voted to incorporate and took as the new town's name the name of Dothan after it was discovered that a "Poplar Head" post office already existed in northern Alabama. The city of Dothan was incorporated on November 11, 1885.

Original inhabitants were the Alabama and Creek Native American tribes.

Hyman Blumberg settled in Dothan in 1892 and started a retail apparel business. He married his sweetheart from Baltimore, Esther Blumberg, and together they had six sons and one daughter, all of whom were active in building the largest department store in southeast Alabama. It was the first store in Dothan to install a moving escalator; people would come from many miles away just to ride this new innovation. Blumberg's and Sons was the first full line department store in Dothan and drew customers from as far away as Georgia and Florida. The store was closed in 1975, but the Blumbergs remain a prominent family in Dothan.