PA 25 begins at an intersection with US 209 in the borough of Millersburg in Dauphin County, heading northeast on two-lane undivided Johnson Street.

The road enters the borough of Berrysburg and becomes West Market Street, passing homes and coming to an intersection with PA 225.

At this point, the route becomes East Market Street and runs past more residences before heading back into Mifflin Township and becoming an unnamed road that passes through open farmland.

The route continues past more homes along with some businesses, becoming a divided highway as it passes through the center of town and becomes East Market Street.

[2][3] PA 25 crosses into Hubley Township in Schuylkill County and becomes West Main Street, continuing through areas of farms with some woodland and homes.

The route continues into Hegins Township and becomes West Main Street, heading into the community of Valley View, where it passes several homes along with a few businesses.

PA 25 curves to the southeast and crosses Swatara Road before coming to its eastern terminus at another intersection with US 209 in Newtown.