PA 166 begins at an intersection with US 119 in Springhill Township just north of the confluence of the Monongahela and Cheat Rivers at the borough of Point Marion.

The route passes through forested areas with a few homes and farms, turning north and reaching the Friendship Hill National Historic Site.

Here, the route passes through the residential community of New Geneva, with Norfolk Southern's Loveridge Secondary railroad line running in between the road and the Monongahela River.

Upon crossing into German Township and curving northeast away from the river, PA 166 becomes Masontown Woodside Road and passes through more woodland.

The route passes through the residential community of Edenborn before continuing north through forested areas with some homes on Ball Hill Road.