Prior to a realignment in 2017, PA 381 briefly turned southeast to form a concurrency with US 40 due to an offset intersection which was eliminated.

The route curves east and leaves the state park as it heads north through wooded areas of homes before passing through an agricultural clearing.

PA 381 runs through more forested areas and passes through Kauffman, at which point it heads to the east of Fallingwater, a house designed by architect Frank Lloyd Wright.

The road continues through forests with some farm fields and homes, heading into Springfield Township at the point it crosses Laurel Run.

At this point, the route turns northeast to form a concurrency with PA 711 on Indian Creek Valley Road, continuing through wooded areas with some farm fields and residences.

The road crosses into Saltlick Township and passes through Frogtown, at which point it runs a short distance to the northwest of Indian Creek.

[2][3] PA 381/PA 711 enters Donegal Township in Westmoreland County and becomes Jones Mill Road, heading through wooded areas with some residential development.