
Lyon Hall was built with slave labor for its first resident, George Gaines Lyon. He had moved from Mobile, Mobile County, to Demopolis with his wife, Annie Glover Lyon, to practice law with his uncle Francis Strother Lyon. Francis served in the U.S. Congress in the 1830s, was notable in Alabama politics, and lived at nearby Bluff Hall. George Lyon also was a planter who would later serve the Confederate and Alabama governments. Lyon was a member of a prominent Alabama family that included businessman, military figure, and politician George Strother Gaines and noted U.S. general Edmund Pendleton Gaines.

The interior of the house features a wide central hall, double parlors, drawing and dining rooms, a bedroom, kitchen, and other rooms. A staircase leads to the second floor and four bedrooms as well as dressing rooms. The house has not been altered significantly, save for electricity and indoor plumbing. The interior was decorated with furnishings the family ordered from New York, and many of these original pieces can be seen on display today.
The house remained in the Lyon-Lamar family almost 150 years, with its deed split among various family members. George Gaines Lamar, the great-grandson of Annie Glover Lyon, was the final resident of the house. He bequeathed his majority share and estate to first cousin Helen Nation. She then deeded her ownership to the MCHS and provided funds per Lamar's estate to begin the preservation of the house and grounds, which had fallen into disrepair. Nation also created and endowed the Lyon Hall Charitable Foundation in memory of her aunt Annie Gaines Lyon, to help with the house's maintenance and preservation.

Today, the MCHS gives tours of Lyon Hall by appointment and allows the property to be rented out as an event space. It is located at 102 South Main Avenue, Demopolis. The MCHS, headquartered in the 1870s Laird Cottage, also manages nearby Bluff Hall.