PA 225 begins at an interchange with the US 22/US 322 freeway in Middle Paxton Township, Dauphin County, heading east on Peters Mountain Road, a four-lane divided highway.

The road briefly enters the borough of Dauphin, where it turns north back into Middle Paxton Township and heads through rural areas of homes.

At the summit, the road heads into Halifax Township and passes under a bridge carrying the Appalachian Trail, making a hairpin turn to the west to descend the mountain.

The route runs north-northeast before passing through the residential communities of Powells Valley and Matamoras, heading more to the north at this point.

The road gains a center left-turn lane and heads north through rural areas of homes and businesses.

The two routes continue into the borough of Halifax and become South 4th Street, losing the center left-turn lane and passing several homes.

[2][3][4] PA 225 heads into the commercial center of town and intersects US 209, becoming North Market Street at this point and passing more homes along with a few businesses.

The route heads back into Mifflin Township and becomes an unnamed road, running through more farm fields with some homes and curving to the northeast.

[2][3] PA 225 crosses the Mahantango Creek into Lower Mahanoy Township in Northumberland County, becoming an unnamed road and curving north into a mix of farmland and woodland.

PA 225 crosses the creek and passes through Dornsife, curving to the east before turning northeast into farmland with some woods and homes.

PA 225 continues into Coal Township and becomes Corporal David Whitmer Highway, running through the residential community of Klingers.

[9] In the 1930s, the northern terminus was cut back to US 122 (now PA 61) in Shamokin, with the former alignment between Shamokin and Line Mountain becoming part of PA 125, while the route was extended south from Berrysburg to US 11/US 15/US 22/US 322 (Allegheny Street) in Dauphin, following its current alignment south to Dauphin before heading through the borough on Claster Boulevard and Lower Erie Street.