The western terminus of the highway is at an intersection with U.S. Route 29 (US 29) in the southwestern part of Andalusia.

State Route 100 (SR 100) begins at an intersection with US 29 in the southwestern part of Andalusia.

It proceeds east on two-lane undivided Sanford Road, passing through residential areas and crossing the Three Notch Railroad.

The highway continues past more residences before turning northeast into wooded areas, eventually reaching its eastern terminus at an intersection with US 84.

[citation needed] SR 100 was designated in 1962 along the route of a southern bypass of Andalusia.