In 1918, the word "Old" was incorporated into the name to eliminate confusion with Appleton City in St. Clair County, Missouri.

In the 1780s, Pierre Louis Lorimier, a French Canadian who had worked as an Indian-interpreter for the British, found it in his best interest to leave the American states.

Like Lorimier, the Shawnee and Delaware Indians had sided with the British, and found themselves in an unsavory situation.

Lorimier appealed for land grants from the Spanish authorities for the settlement of Shawnee and Delaware Indians from American territory.

[5] The Spanish granted Lorimier two large tracts of land in the Apple creek watershed, with the intention of the Shawnee and Delaware acting as a buffer against the Osage Indians, who were not on friendly terms with the Spanish authorities.

Culturally, the Shawnee and Delaware had largely adopted French and American ways and lifestyles, and had built granaries and barns for the storing of their crops and housing of their cattle and horses.

The Shawnee and Delaware built their log homes in the French fashion with posts set together and interstices filled with clay, with wood shingled roofs.

[6][7] In the early 1800s American settlers began encroaching on the Shawnee and Delaware lands around Apple Creek.

In 1809, harassment and stealing by American settlers eventually drove the Shawnee and Delaware to visit the territorial governor Meriwether Lewis and pressed their "long-expressed wish" to exchange of their lands in the Apple Creek watershed with lands farther west.

By 1816, the encroachment by white settlers left the US Federal Government no choice but to relocate the Shawnee and Delaware to lands further west.

[11] In 1982, a flood on Apple creek destroyed McClain Mill and Old Appleton's original bridge.

[13] Old Appleton is located on the south bank of the Apple Creek and the northern border of Cape Girardeau County.

[14] According to the United States Census Bureau, the village has a total area of 0.12 square miles (0.31 km2), all land.