SR 100 begins as a primary highway in West Tennessee in Hardeman County at an intersection with US 64/SR 15 in Whiteville.

Then SR 100 leaves Whiteville heading east but slightly northward before crossing the Hatchie River.

The highway then leaves Decaturville and continues northeast to Perryville, where it crosses a bridge over the Beech River before coming to an intersection and becomes concurrent with US 412/SR 20.

US 412/SR 20/SR 100 then leaves Linden and passes through Chestnut Grove before coming to a Y-Intersection where SR 100 splits off from US 412/SR 20 and goes northeast, becoming a primary highway and crossing into Hickman County.

[1] Prior to construction of Interstate 40, SR 100 (in conjunction US 64 between Bartlett and Whiteville) was a customarily traveled route between Memphis and Nashville but today serves primarily local traffic.