PA 49 begins at an intersection with
PA 44 north of the borough of
Coudersport in
Eulalia Township,
Potter County, heading east on a two-lane undivided road. The route runs through forested areas of hills with some farm fields and homes to the north of the
Allegheny River, turning northeast and crossing into
Hebron Township. The road curves east and enters
Allegany Township, curving back to the northeast and turning east again at Colesburg. PA 49 winds east through more rural areas, turning to the northeast away from the river into more agricultural areas with some woods and homes, running through Raymond. The road heads into
Ulysses Township and comes to an intersection with
PA 449 in the community of
Gold. PA 49 enters
Westfield Township in
Tioga County and passes through the residential community of Potter Brook before heading through open agricultural areas with a few homes, crossing the Cowanesque River twice and passing south of
Cowanesque Valley Junior Senior High School. The road crosses into the borough of
Westfield and becomes West Main Street, passing residences and a few businesses, coming to another crossing of the Cowanesque River. The route heads into the commercial downtown of Westfield and intersects the northern terminus of
PA 349, becoming East Main Street. PA 49 continues east-northeast near a few homes and crosses back into Westfield Township, heading into farmland with some residences and crossing the river again. The road continues through more rural areas with some homes, passing through
Cowanesque before coming to an intersection with
PA 249 in Phillips. Here, PA 249 turns northeast to form a
concurrency with PA 49, heading through farmland and woodland with some residences. The road briefly passes through
Brookfield Township before heading into
Deerfield Township. PA 249 splits from PA 49 by turning to the north, and PA 49 crosses the
Troups Creek into the borough of
Knoxville, becoming West Main Street. The road heads through residential areas with some businesses, becoming East Main Street as it continues through the town. ==Major intersections==