It is not clear why or how Perryville came to be selected as the county seat of Perry County, Missouri, but on August 7, 1821, Bernard Layton deeded to the commissioners in exchange for one town lot. Fifty-three of the 99 town lots were sold for $1,486.25, which was used to build the first courthouse. The one existing today is actually the third such structure. It was built in 1904 at a cost of $30,000.
There were two early stores in Perryville. The first, a log structure, was built by Ferdinand Rozier, Sr. on the north side of the square. The second, built by Levi Block, was a two-story building. The upper story served as the first town hall for the small settlement. Perryville was first incorporated in 1837, but records show the incorporation was allowed to lapse. In the early 19th century, Henry Burns built a home on South Spring Street. Later, William P. Faherty bought the house, which is now a museum operated by the Perry County Historical Society.
As both merchandisers and consumers grew in sophistication, so did the types of establishments in the county. Built in 1843, the Hoose Hotel, often called the "white house", was a prominent structure in early commercial days. The Hoose Hotel was located at the site presently occupied by Eagle Bank and Trust Co. and The Total Package and served as a hotel, a brewery and an auction block.
In 1856, the town was again incorporated and by 1874 it had its first fire engine. Fourth Class City status was attained in 1879 and the following year Charles A. Weber was elected its first mayor. With the building of the Chester, Perryville and Ste. Genevieve Railway, prosperity came.
Largely because of its role as the seat of county government and because of its central location, Perryville began to develop as the major commercial and service center in Perry County. The population jumped from 897 in 1890 to 1275 in 1900. In 1893 the telephone arrived.
The first horseless carriage, deemed a "locomobile" by The Perry County Republican newspaper, was reported in Perryville in 1903. The first power plant was built in 1913 to provide Perryville with electric lights. This building is currently being renovated by the Perry Art Alliance. In 1923, the Chamber of Commerce was formed, and Perryville launched its first industrial development offensive by raising $100,000 to build an industrial building in the hope of persuading International Shoe Company in St. Louis to open a Perryville plant. The venture was successful and the opening of the International plant spurred a cycle of growth which included the paving of city streets and a host of new businesses and city services.
In 1940, a second International production facility, known as the Kiefner Branch, opened in Perryville. However, in 1964 an economic downturn forced the closing of International's original Magnolia branch plant.
The loss of 250 jobs in the Magnolia plant closing heightened interest in a more diverse industrial base. The efforts of the Chamber of Commerce, Perryville Development Corporation, and city officials led to the development of the Perryville Industrial Park and the establishment of an Enterprise Zone. The City of Perryville hired its first City Administrator in 1976. The Perry County Industrial Development Authority was established in 1983. Over time, tenants in the Perryville Industrial Park include TG Missouri Corporation, T-N-T Plastics, Wilkes Integrated Packaging, Falcon Foam, Industrial Foam Products, Perry County Sheltered Workshop and Missouri Corrugated Box.
Among contemporary manufacturers in Perryville is Gilster-Mary Lee Corporation, with two facilities (a baking mix plant and a breakfast cereal plant). Also in the Perrville area are