Wendell was settled in the 1850s, when farmers in Granville County were victims of a blight that came to be known as the Granville County Wilt. Their tobacco crops failed, and they chose to move to a new location with more fertile land for their crops.

The first post office was built in 1891, and has been restored by the Wendell Historical Society. The oldest institution in Wendell is Hephzibah Baptist Church, founded in 1809. The first newspaper was the Wendell Clarion, founded in 1911, which was succeeded by the Gold Leaf Farmer and currently the Eastern Wake News. Wendell was incorporated in 1903.

Wendell has four buildings and one district that are listed on the National Register of Historic Places. These are the Dr. Thomas H. Avera House, Harmony Plantation, Riley Hill School, Sunnyside, and the Wendell Commercial Historic District.