Herculaneum was laid out by Moses Austin and Samuel Hammond in 1808 as a shipping point on the Mississippi River closer to Austin's lead mines in Potosi than was Ste. Genevieve. The town was named after the ancient Roman town of Herculaneum, destroyed by the eruption of Mt. Vesuvius, and Austin is said to have chosen the name because the limestone ledges overlooking the Mississippi River resembled a Roman amphitheatre. Shot towerswere constructed next to the bluffs to manufacture lead ammunition, and lead cannonballs from Herculaneum were used in the War of 1812. Lead smelting by the Doe Run Company is still the major industry in this town.

Dunklin R-5 School District (Herculaneum, Pevely and Horine) is based in Herculaneum with Administrative Offices located at 400 Joachim Avenue. The Herculaneum High School and the Senn-Thomas Middle School (grades 6-8) are both located in the city of Herculaneum. The Pevely Elementary School (grades K-5) are located in Pevely, Missouri.

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