The town took its name from an old Indian village which once stood in the area; its name in turn is derived from the Chickasaw language purported to mean "dismal prairie".

In 1840, Tobias and Allison Furr moved to the vicinity of Toccopola from Mecklenburg County, North Carolina and built a water mill and store.

The college closed in 1907 after the Gulf, Mobile and Northern Railroad bypassed Toccopola in favor of Pontotoc, which caused many citizens to leave the community.

[6] According to the United States Census Bureau, the town has a total area of 1.5 square miles (3.9 km2), all land.

Mississippi Highway 334 passes directly through Toccopola, connecting it with Oxford to the west, and Pontotoc to the east.