PA 349 begins at an intersection with US 6 in Gaines Township, heading north on a two-lane undivided road.

The route heads through forested areas of mountains within State Game Lands Number 208, running to the west of Long Run.

Farther north, the road enters Clymer Township and passes through Davis as it turns northeast into areas of farmland and wooded mountains, heading away from Long Run and following Elklick Run.

PA 349 reaches the residential community of Sabinsville and curves north again as it heads into Westfield Township.

Here, the route passes through more rural areas of farms and woods with a few homes, running to the west of Mill Creek.