SR 227 begins in Wayne County at the Alabama state line in the Cypress Inn community, where it continues south as Alabama State Route 157 (SR 157).

SR 227 immediately makes a sharp right turn at an intersection with Big Cypress Road, which provides access to the Natchez Trace Parkway, before going east through a mix of farmland and wooded areas for several miles to the community of Fairview, where it has a short concurrency with SR 13.

It then enters the Highland Rim and winds its way east through mountains to cross into Lawrence County.

[2] The highway almost immediately passes through the town of Iron City, where it has an intersection with SR 242 and crosses over Shoal Creek, before going east through mountains to the town of Saint Joseph where it comes to an intersection and becomes concurrent with US 43/SR 6.

They head northeast through farmland for a few miles to the town of Loretto, where SR 227 breaks off and turns southeast.