The northern terminus is at U.S. Route 19 (US 19)/PA 21 in Waynesburg, approximately 1 mile (1.6 km) east of PA 18.

PA 218 begins at the West Virginia border in Wayne Township, where the road continues south into that state as WV 218.

From the state line, the route heads north on two-lane undivided Smith Creek Road, passing through forested areas with a few clearings and rural homes.

PA 218 reaches the community of Blairtown and crosses the South Fork Tenmile Creek into the borough of Waynesburg.

Here, the road becomes South Morgan Street and crosses Norfolk Southern's Mon Line, heading into residential and commercial areas.